Cone Genesis Tracing by the Chrnb4-EGFP Mouse Line: Evidences of Cellular Material Fusion after Cone Precursor Transplantation
Identifieur interne : 000A38 ( Pmc/Curation ); précédent : 000A37; suivant : 000A39Cone Genesis Tracing by the Chrnb4-EGFP Mouse Line: Evidences of Cellular Material Fusion after Cone Precursor Transplantation
Auteurs : Sarah Decembrini [Suisse] ; Catherine Martin [Suisse] ; Florian Sennlaub [France] ; Sylvain Chemtob [Canada] ; Martin Biel [Allemagne] ; Marijana Samardzija [Suisse] ; Alexandre Moulin [Suisse] ; Francine Behar-Cohen [Suisse] ; Yvan Arsenijevic [Suisse]Source :
- Molecular Therapy [ 1525-0016 ] ; 2017.
Abstract
The cone function is essential to mediate high visual acuity, color vision, and daylight vision. Inherited cone dystrophies and age-related macular degeneration affect a substantial percentage of the world population. To identify and isolate the most competent cells for transplantation and integration into the retina, cone tracing during development would be an important added value. To that aim, the
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DOI: 10.1016/j.ymthe.2016.12.015
PubMed: 28143742
PubMed Central: 5363218
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cone Genesis Tracing by the <italic>Chrnb4</italic>-EGFP Mouse Line: Evidences of Cellular Material Fusion after Cone Precursor Transplantation</title><author><name sortKey="Decembrini, Sarah" sort="Decembrini, Sarah" uniqKey="Decembrini S" first="Sarah" last="Decembrini">Sarah Decembrini</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Martin, Catherine" sort="Martin, Catherine" uniqKey="Martin C" first="Catherine" last="Martin">Catherine Martin</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Sennlaub, Florian" sort="Sennlaub, Florian" uniqKey="Sennlaub F" first="Florian" last="Sennlaub">Florian Sennlaub</name><affiliation wicri:level="1"><nlm:aff id="aff2">Sorbonne Universités, UPMC/Univ Paris 06, UMRS 968, INSERM, U968, Institut de la Vision, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC/Univ Paris 06, UMRS 968, INSERM, U968, Institut de la Vision, 75012 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Chemtob, Sylvain" sort="Chemtob, Sylvain" uniqKey="Chemtob S" first="Sylvain" last="Chemtob">Sylvain Chemtob</name><affiliation wicri:level="1"><nlm:aff id="aff3">Departments of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste. Justine Research Center, Montreal, QC H3T1C5, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste. 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Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, 8952 Schlieren</wicri:regionArea></affiliation></author><author><name sortKey="Moulin, Alexandre" sort="Moulin, Alexandre" uniqKey="Moulin A" first="Alexandre" last="Moulin">Alexandre Moulin</name><affiliation wicri:level="1"><nlm:aff id="aff6">Pathology Laboratory, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Pathology Laboratory, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Behar Cohen, Francine" sort="Behar Cohen, Francine" uniqKey="Behar Cohen F" first="Francine" last="Behar-Cohen">Francine Behar-Cohen</name><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Arsenijevic, Yvan" sort="Arsenijevic, Yvan" uniqKey="Arsenijevic Y" first="Yvan" last="Arsenijevic">Yvan Arsenijevic</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, 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Sarah" sort="Decembrini, Sarah" uniqKey="Decembrini S" first="Sarah" last="Decembrini">Sarah Decembrini</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Martin, Catherine" sort="Martin, Catherine" uniqKey="Martin C" first="Catherine" last="Martin">Catherine Martin</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Sennlaub, Florian" sort="Sennlaub, Florian" uniqKey="Sennlaub F" first="Florian" last="Sennlaub">Florian Sennlaub</name><affiliation wicri:level="1"><nlm:aff id="aff2">Sorbonne Universités, UPMC/Univ Paris 06, UMRS 968, INSERM, U968, Institut de la Vision, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC/Univ Paris 06, UMRS 968, INSERM, U968, Institut de la Vision, 75012 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Chemtob, Sylvain" sort="Chemtob, Sylvain" uniqKey="Chemtob S" first="Sylvain" last="Chemtob">Sylvain Chemtob</name><affiliation wicri:level="1"><nlm:aff id="aff3">Departments of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste. Justine Research Center, Montreal, QC H3T1C5, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste. Justine Research Center, Montreal, QC H3T1C5</wicri:regionArea></affiliation></author><author><name sortKey="Biel, Martin" sort="Biel, Martin" uniqKey="Biel M" first="Martin" last="Biel">Martin Biel</name><affiliation wicri:level="1"><nlm:aff id="aff4">Center for Integrated Protein Science Munich CIPSM, Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 München, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Center for Integrated Protein Science Munich CIPSM, Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 München</wicri:regionArea></affiliation></author><author><name sortKey="Samardzija, Marijana" sort="Samardzija, Marijana" uniqKey="Samardzija M" first="Marijana" last="Samardzija">Marijana Samardzija</name><affiliation wicri:level="1"><nlm:aff id="aff5">Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, 8952 Schlieren, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, 8952 Schlieren</wicri:regionArea></affiliation></author><author><name sortKey="Moulin, Alexandre" sort="Moulin, Alexandre" uniqKey="Moulin A" first="Alexandre" last="Moulin">Alexandre Moulin</name><affiliation wicri:level="1"><nlm:aff id="aff6">Pathology Laboratory, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Pathology Laboratory, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Behar Cohen, Francine" sort="Behar Cohen, Francine" uniqKey="Behar Cohen F" first="Francine" last="Behar-Cohen">Francine Behar-Cohen</name><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Arsenijevic, Yvan" sort="Arsenijevic, Yvan" uniqKey="Arsenijevic Y" first="Yvan" last="Arsenijevic">Yvan Arsenijevic</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne</wicri:regionArea></affiliation></author></analytic><series><title level="j">Molecular Therapy</title><idno type="ISSN">1525-0016</idno><idno type="eISSN">1525-0024</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The cone function is essential to mediate high visual acuity, color vision, and daylight vision. Inherited cone dystrophies and age-related macular degeneration affect a substantial percentage of the world population. To identify and isolate the most competent cells for transplantation and integration into the retina, cone tracing during development would be an important added value. To that aim, the <italic>Chrnb4</italic>-EGFP mouse line was characterized throughout retinogenesis. It revealed a sub-population of early retinal progenitors expressing the reporter gene that is progressively restricted to mature cones during retina development. The presence of the native CHRNB4 protein was confirmed in EGFP-positive cells, and it presents a similar pattern in the human retina. Sub-retinal transplantations of distinct subpopulations of <italic>Chrnb4</italic>-EGFP-expressing cells revealed the embryonic day 15.5 high-EGFP population the most efficient cells to interact with host retinas to provoke the appearance of EGFP-positive cones in the photoreceptor layer. Importantly, transplantations into the DsRed retinas revealed material exchanges between donor and host retinas, as >80% of transplanted EGFP-positive cones also were DsRed positive. Whether this cell material fusion is of significant therapeutic advantage requires further thorough investigations. The <italic>Chrnb4</italic>-EGFP mouse line definitely opens new research perspectives in cone genesis and retina repair.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Roosing, S" uniqKey="Roosing S">S. Roosing</name></author><author><name sortKey="Thiadens, A A" uniqKey="Thiadens A">A.A. Thiadens</name></author><author><name sortKey="Hoyng, C B" uniqKey="Hoyng C">C.B. Hoyng</name></author><author><name sortKey="Klaver, C C" uniqKey="Klaver C">C.C. Klaver</name></author><author><name sortKey="Den Hollander, A I" uniqKey="Den Hollander A">A.I. den Hollander</name></author><author><name sortKey="Cremers, F P" uniqKey="Cremers F">F.P. Cremers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ait Ali, N" uniqKey="Ait Ali N">N. Aït-Ali</name></author><author><name sortKey="Fridlich, R" uniqKey="Fridlich R">R. Fridlich</name></author><author><name sortKey="Millet Puel, G" uniqKey="Millet Puel G">G. Millet-Puel</name></author><author><name sortKey="Clerin, E" uniqKey="Clerin E">E. Clérin</name></author><author><name sortKey="Delalande, F" uniqKey="Delalande F">F. Delalande</name></author><author><name sortKey="Jaillard, C" uniqKey="Jaillard C">C. Jaillard</name></author><author><name sortKey="Blond, F" uniqKey="Blond F">F. Blond</name></author><author><name sortKey="Perrocheau, L" uniqKey="Perrocheau L">L. Perrocheau</name></author><author><name sortKey="Reichman, S" uniqKey="Reichman S">S. Reichman</name></author><author><name sortKey="Byrne, L C" uniqKey="Byrne L">L.C. Byrne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mohand Said, S" uniqKey="Mohand Said S">S. Mohand-Said</name></author><author><name sortKey="Deudon Combe, A" uniqKey="Deudon Combe A">A. Deudon-Combe</name></author><author><name sortKey="Hicks, D" uniqKey="Hicks D">D. Hicks</name></author><author><name sortKey="Simonutti, M" uniqKey="Simonutti M">M. Simonutti</name></author><author><name sortKey="Forster, V" uniqKey="Forster V">V. Forster</name></author><author><name sortKey="Fintz, A C" uniqKey="Fintz A">A.C. Fintz</name></author><author><name sortKey="Leveillard, T" uniqKey="Leveillard T">T. Léveillard</name></author><author><name sortKey="Dreyfus, H" uniqKey="Dreyfus H">H. Dreyfus</name></author><author><name sortKey="Sahel, J A" uniqKey="Sahel J">J.A. Sahel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Punzo, C" uniqKey="Punzo C">C. Punzo</name></author><author><name sortKey="Kornacker, K" uniqKey="Kornacker K">K. Kornacker</name></author><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Byrne, L C" uniqKey="Byrne L">L.C. Byrne</name></author><author><name sortKey="Dalkara, D" uniqKey="Dalkara D">D. Dalkara</name></author><author><name sortKey="Luna, G" uniqKey="Luna G">G. Luna</name></author><author><name sortKey="Fisher, S K" uniqKey="Fisher S">S.K. Fisher</name></author><author><name sortKey="Clerin, E" uniqKey="Clerin E">E. Clérin</name></author><author><name sortKey="Sahel, J A" uniqKey="Sahel J">J.A. Sahel</name></author><author><name sortKey="Leveillard, T" uniqKey="Leveillard T">T. Léveillard</name></author><author><name sortKey="Flannery, J G" uniqKey="Flannery J">J.G. Flannery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiong, W" uniqKey="Xiong W">W. Xiong</name></author><author><name sortKey="Maccoll Garfinkel, A E" uniqKey="Maccoll Garfinkel A">A.E. MacColl Garfinkel</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Benowitz, L I" uniqKey="Benowitz L">L.I. Benowitz</name></author><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Milam, A H" uniqKey="Milam A">A.H. Milam</name></author><author><name sortKey="Li, Z Y" uniqKey="Li Z">Z.Y. Li</name></author><author><name sortKey="Fariss, R N" uniqKey="Fariss R">R.N. Fariss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hafler, B P" uniqKey="Hafler B">B.P. Hafler</name></author><author><name sortKey="Surzenko, N" uniqKey="Surzenko N">N. Surzenko</name></author><author><name sortKey="Beier, K T" uniqKey="Beier K">K.T. Beier</name></author><author><name sortKey="Punzo, C" uniqKey="Punzo C">C. Punzo</name></author><author><name sortKey="Trimarchi, J M" uniqKey="Trimarchi J">J.M. Trimarchi</name></author><author><name sortKey="Kong, J H" uniqKey="Kong J">J.H. Kong</name></author><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, S" uniqKey="Chen S">S. Chen</name></author><author><name sortKey="Wang, Q L" uniqKey="Wang Q">Q.L. Wang</name></author><author><name sortKey="Nie, Z" uniqKey="Nie Z">Z. Nie</name></author><author><name sortKey="Sun, H" uniqKey="Sun H">H. Sun</name></author><author><name sortKey="Lennon, G" uniqKey="Lennon G">G. Lennon</name></author><author><name sortKey="Copeland, N G" uniqKey="Copeland N">N.G. Copeland</name></author><author><name sortKey="Gilbert, D J" uniqKey="Gilbert D">D.J. Gilbert</name></author><author><name sortKey="Jenkins, N A" uniqKey="Jenkins N">N.A. Jenkins</name></author><author><name sortKey="Zack, D J" uniqKey="Zack D">D.J. Zack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nishida, A" uniqKey="Nishida A">A. Nishida</name></author><author><name sortKey="Furukawa, A" uniqKey="Furukawa A">A. Furukawa</name></author><author><name sortKey="Koike, C" uniqKey="Koike C">C. Koike</name></author><author><name sortKey="Tano, Y" uniqKey="Tano Y">Y. Tano</name></author><author><name sortKey="Aizawa, S" uniqKey="Aizawa S">S. Aizawa</name></author><author><name sortKey="Matsuo, I" uniqKey="Matsuo I">I. Matsuo</name></author><author><name sortKey="Furukawa, T" uniqKey="Furukawa T">T. Furukawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emerson, M M" uniqKey="Emerson M">M.M. Emerson</name></author><author><name sortKey="Surzenko, N" uniqKey="Surzenko N">N. Surzenko</name></author><author><name sortKey="Goetz, J J" uniqKey="Goetz J">J.J. Goetz</name></author><author><name sortKey="Trimarchi, J" uniqKey="Trimarchi J">J. Trimarchi</name></author><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hyatt, G A" uniqKey="Hyatt G">G.A. Hyatt</name></author><author><name sortKey="Dowling, J E" uniqKey="Dowling J">J.E. Dowling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brzezinski, J A" uniqKey="Brzezinski J">J.A. Brzezinski</name></author><author><name sortKey="Reh, T A" uniqKey="Reh T">T.A. Reh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author><author><name sortKey="Austin, C P" uniqKey="Austin C">C.P. Austin</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="Alexiades, M" uniqKey="Alexiades M">M. Alexiades</name></author><author><name sortKey="Ezzeddine, D" uniqKey="Ezzeddine D">D. Ezzeddine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, I" uniqKey="Jones I">I. Jones</name></author><author><name sortKey="Ng, L" uniqKey="Ng L">L. Ng</name></author><author><name sortKey="Liu, H" uniqKey="Liu H">H. Liu</name></author><author><name sortKey="Forrest, D" uniqKey="Forrest D">D. Forrest</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lipinski, D M" uniqKey="Lipinski D">D.M. Lipinski</name></author><author><name sortKey="Yusuf, M" uniqKey="Yusuf M">M. Yusuf</name></author><author><name sortKey="Barnard, A R" uniqKey="Barnard A">A.R. Barnard</name></author><author><name sortKey="Damant, C" uniqKey="Damant C">C. Damant</name></author><author><name sortKey="Charbel Issa, P" uniqKey="Charbel Issa P">P. Charbel Issa</name></author><author><name sortKey="Singh, M S" uniqKey="Singh M">M.S. Singh</name></author><author><name sortKey="Lee, E" uniqKey="Lee E">E. Lee</name></author><author><name sortKey="Davies, W L" uniqKey="Davies W">W.L. Davies</name></author><author><name sortKey="Volpi, E V" uniqKey="Volpi E">E.V. Volpi</name></author><author><name sortKey="Maclaren, R E" uniqKey="Maclaren R">R.E. MacLaren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riesenberg, A N" uniqKey="Riesenberg A">A.N. Riesenberg</name></author><author><name sortKey="Liu, Z" uniqKey="Liu Z">Z. Liu</name></author><author><name sortKey="Kopan, R" uniqKey="Kopan R">R. Kopan</name></author><author><name sortKey="Brown, N L" uniqKey="Brown N">N.L. Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samardzija, M" uniqKey="Samardzija M">M. Samardzija</name></author><author><name sortKey="Tanimoto, N" uniqKey="Tanimoto N">N. Tanimoto</name></author><author><name sortKey="Kostic, C" uniqKey="Kostic C">C. Kostic</name></author><author><name sortKey="Beck, S" uniqKey="Beck S">S. Beck</name></author><author><name sortKey="Oberhauser, V" uniqKey="Oberhauser V">V. Oberhauser</name></author><author><name sortKey="Joly, S" uniqKey="Joly S">S. Joly</name></author><author><name sortKey="Thiersch, M" uniqKey="Thiersch M">M. Thiersch</name></author><author><name sortKey="Fahl, E" uniqKey="Fahl E">E. Fahl</name></author><author><name sortKey="Arsenijevic, Y" uniqKey="Arsenijevic Y">Y. Arsenijevic</name></author><author><name sortKey="Von Lintig, J" uniqKey="Von Lintig J">J. von Lintig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smiley, S" uniqKey="Smiley S">S. Smiley</name></author><author><name sortKey="Nickerson, P E" uniqKey="Nickerson P">P.E. Nickerson</name></author><author><name sortKey="Comanita, L" uniqKey="Comanita L">L. Comanita</name></author><author><name sortKey="Daftarian, N" uniqKey="Daftarian N">N. Daftarian</name></author><author><name sortKey="El Sehemy, A" uniqKey="El Sehemy A">A. El-Sehemy</name></author><author><name sortKey="Tsai, E L" uniqKey="Tsai E">E.L. Tsai</name></author><author><name sortKey="Matan Lithwick, S" uniqKey="Matan Lithwick S">S. Matan-Lithwick</name></author><author><name sortKey="Yan, K" uniqKey="Yan K">K. Yan</name></author><author><name sortKey="Thurig, S" uniqKey="Thurig S">S. Thurig</name></author><author><name sortKey="Touahri, Y" uniqKey="Touahri Y">Y. Touahri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Siegert, S" uniqKey="Siegert S">S. Siegert</name></author><author><name sortKey="Scherf, B G" uniqKey="Scherf B">B.G. Scherf</name></author><author><name sortKey="Del Punta, K" uniqKey="Del Punta K">K. Del Punta</name></author><author><name sortKey="Didkovsky, N" uniqKey="Didkovsky N">N. Didkovsky</name></author><author><name sortKey="Heintz, N" uniqKey="Heintz N">N. Heintz</name></author><author><name sortKey="Roska, B" uniqKey="Roska B">B. Roska</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Szikra, T" uniqKey="Szikra T">T. Szikra</name></author><author><name sortKey="Trenholm, S" uniqKey="Trenholm S">S. Trenholm</name></author><author><name sortKey="Drinnenberg, A" uniqKey="Drinnenberg A">A. Drinnenberg</name></author><author><name sortKey="Juttner, J" uniqKey="Juttner J">J. Jüttner</name></author><author><name sortKey="Raics, Z" uniqKey="Raics Z">Z. Raics</name></author><author><name sortKey="Farrow, K" uniqKey="Farrow K">K. Farrow</name></author><author><name sortKey="Biel, M" uniqKey="Biel M">M. Biel</name></author><author><name sortKey="Awatramani, G" uniqKey="Awatramani G">G. Awatramani</name></author><author><name sortKey="Clark, D A" uniqKey="Clark D">D.A. Clark</name></author><author><name sortKey="Sahel, J A" uniqKey="Sahel J">J.A. Sahel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Albuquerque, E X" uniqKey="Albuquerque E">E.X. Albuquerque</name></author><author><name sortKey="Pereira, E F" uniqKey="Pereira E">E.F. Pereira</name></author><author><name sortKey="Castro, N G" uniqKey="Castro N">N.G. Castro</name></author><author><name sortKey="Alkondon, M" uniqKey="Alkondon M">M. Alkondon</name></author><author><name sortKey="Reinhardt, S" uniqKey="Reinhardt S">S. Reinhardt</name></author><author><name sortKey="Schroder, H" uniqKey="Schroder H">H. Schröder</name></author><author><name sortKey="Maelicke, A" uniqKey="Maelicke A">A. Maelicke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cayouette, M" uniqKey="Cayouette M">M. Cayouette</name></author><author><name sortKey="Barres, B A" uniqKey="Barres B">B.A. Barres</name></author><author><name sortKey="Raff, M" uniqKey="Raff M">M. Raff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Merkle, F T" uniqKey="Merkle F">F.T. Merkle</name></author><author><name sortKey="Alvarez Buylla, A" uniqKey="Alvarez Buylla A">A. Alvarez-Buylla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carter Dawson, L D" uniqKey="Carter Dawson L">L.D. Carter-Dawson</name></author><author><name sortKey="Lavail, M M" uniqKey="Lavail M">M.M. LaVail</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rapaport, D H" uniqKey="Rapaport D">D.H. Rapaport</name></author><author><name sortKey="Wong, L L" uniqKey="Wong L">L.L. Wong</name></author><author><name sortKey="Wood, E D" uniqKey="Wood E">E.D. Wood</name></author><author><name sortKey="Yasumura, D" uniqKey="Yasumura D">D. Yasumura</name></author><author><name sortKey="Lavail, M M" uniqKey="Lavail M">M.M. LaVail</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cepko, C" uniqKey="Cepko C">C. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Turner, D L" uniqKey="Turner D">D.L. Turner</name></author><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roberts, M R" uniqKey="Roberts M">M.R. Roberts</name></author><author><name sortKey="Hendrickson, A" uniqKey="Hendrickson A">A. Hendrickson</name></author><author><name sortKey="Mcguire, C R" uniqKey="Mcguire C">C.R. McGuire</name></author><author><name sortKey="Reh, T A" uniqKey="Reh T">T.A. Reh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barber, A C" uniqKey="Barber A">A.C. Barber</name></author><author><name sortKey="Hippert, C" uniqKey="Hippert C">C. Hippert</name></author><author><name sortKey="Duran, Y" uniqKey="Duran Y">Y. Duran</name></author><author><name sortKey="West, E L" uniqKey="West E">E.L. West</name></author><author><name sortKey="Bainbridge, J W" uniqKey="Bainbridge J">J.W. Bainbridge</name></author><author><name sortKey="Warre Cornish, K" uniqKey="Warre Cornish K">K. Warre-Cornish</name></author><author><name sortKey="Luhmann, U F" uniqKey="Luhmann U">U.F. Luhmann</name></author><author><name sortKey="Lakowski, J" uniqKey="Lakowski J">J. Lakowski</name></author><author><name sortKey="Sowden, J C" uniqKey="Sowden J">J.C. Sowden</name></author><author><name sortKey="Ali, R R" uniqKey="Ali R">R.R. Ali</name></author><author><name sortKey="Pearson, R A" uniqKey="Pearson R">R.A. Pearson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Biel, M" uniqKey="Biel M">M. Biel</name></author><author><name sortKey="Seeliger, M" uniqKey="Seeliger M">M. Seeliger</name></author><author><name sortKey="Pfeifer, A" uniqKey="Pfeifer A">A. Pfeifer</name></author><author><name sortKey="Kohler, K" uniqKey="Kohler K">K. Kohler</name></author><author><name sortKey="Gerstner, A" uniqKey="Gerstner A">A. Gerstner</name></author><author><name sortKey="Ludwig, A" uniqKey="Ludwig A">A. Ludwig</name></author><author><name sortKey="Jaissle, G" uniqKey="Jaissle G">G. Jaissle</name></author><author><name sortKey="Fauser, S" uniqKey="Fauser S">S. Fauser</name></author><author><name sortKey="Zrenner, E" uniqKey="Zrenner E">E. Zrenner</name></author><author><name sortKey="Hofmann, F" uniqKey="Hofmann F">F. Hofmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kinouchi, R" uniqKey="Kinouchi R">R. Kinouchi</name></author><author><name sortKey="Takeda, M" uniqKey="Takeda M">M. Takeda</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L. Yang</name></author><author><name sortKey="Wilhelmsson, U" uniqKey="Wilhelmsson U">U. Wilhelmsson</name></author><author><name sortKey="Lundkvist, A" uniqKey="Lundkvist A">A. Lundkvist</name></author><author><name sortKey="Pekny, M" uniqKey="Pekny M">M. Pekny</name></author><author><name sortKey="Chen, D F" uniqKey="Chen D">D.F. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mears, A J" uniqKey="Mears A">A.J. Mears</name></author><author><name sortKey="Kondo, M" uniqKey="Kondo M">M. Kondo</name></author><author><name sortKey="Swain, P K" uniqKey="Swain P">P.K. Swain</name></author><author><name sortKey="Takada, Y" uniqKey="Takada Y">Y. Takada</name></author><author><name sortKey="Bush, R A" uniqKey="Bush R">R.A. Bush</name></author><author><name sortKey="Saunders, T L" uniqKey="Saunders T">T.L. Saunders</name></author><author><name sortKey="Sieving, P A" uniqKey="Sieving P">P.A. Sieving</name></author><author><name sortKey="Swaroop, A" uniqKey="Swaroop A">A. Swaroop</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samardzija, M" uniqKey="Samardzija M">M. Samardzija</name></author><author><name sortKey="Caprara, C" uniqKey="Caprara C">C. Caprara</name></author><author><name sortKey="Heynen, S R" uniqKey="Heynen S">S.R. Heynen</name></author><author><name sortKey="Willcox Deparis, S" uniqKey="Willcox Deparis S">S. Willcox DeParis</name></author><author><name sortKey="Meneau, I" uniqKey="Meneau I">I. Meneau</name></author><author><name sortKey="Traber, G" uniqKey="Traber G">G. Traber</name></author><author><name sortKey="Agca, C" uniqKey="Agca C">C. Agca</name></author><author><name sortKey="Von Lintig, J" uniqKey="Von Lintig J">J. von Lintig</name></author><author><name sortKey="Grimm, C" uniqKey="Grimm C">C. Grimm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samardzija, M" uniqKey="Samardzija M">M. Samardzija</name></author><author><name sortKey="Grimm, C" uniqKey="Grimm C">C. Grimm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vintersten, K" uniqKey="Vintersten K">K. Vintersten</name></author><author><name sortKey="Monetti, C" uniqKey="Monetti C">C. Monetti</name></author><author><name sortKey="Gertsenstein, M" uniqKey="Gertsenstein M">M. Gertsenstein</name></author><author><name sortKey="Zhang, P" uniqKey="Zhang P">P. Zhang</name></author><author><name sortKey="Laszlo, L" uniqKey="Laszlo L">L. Laszlo</name></author><author><name sortKey="Biechele, S" uniqKey="Biechele S">S. Biechele</name></author><author><name sortKey="Nagy, A" uniqKey="Nagy A">A. Nagy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dyer, M A" uniqKey="Dyer M">M.A. Dyer</name></author><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dyer, M A" uniqKey="Dyer M">M.A. Dyer</name></author><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levine, E M" uniqKey="Levine E">E.M. Levine</name></author><author><name sortKey="Green, E S" uniqKey="Green E">E.S. Green</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pacal, M" uniqKey="Pacal M">M. Pacal</name></author><author><name sortKey="Bremner, R" uniqKey="Bremner R">R. Bremner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Turner, D L" uniqKey="Turner D">D.L. Turner</name></author><author><name sortKey="Snyder, E Y" uniqKey="Snyder E">E.Y. Snyder</name></author><author><name sortKey="Cepko, C L" uniqKey="Cepko C">C.L. Cepko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Watanabe, T" uniqKey="Watanabe T">T. Watanabe</name></author><author><name sortKey="Raff, M C" uniqKey="Raff M">M.C. Raff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maclaren, R E" uniqKey="Maclaren R">R.E. MacLaren</name></author><author><name sortKey="Pearson, R A" uniqKey="Pearson R">R.A. Pearson</name></author><author><name sortKey="Macneil, A" uniqKey="Macneil A">A. MacNeil</name></author><author><name sortKey="Douglas, R H" uniqKey="Douglas R">R.H. Douglas</name></author><author><name sortKey="Salt, T E" uniqKey="Salt T">T.E. Salt</name></author><author><name sortKey="Akimoto, M" uniqKey="Akimoto M">M. Akimoto</name></author><author><name sortKey="Swaroop, A" uniqKey="Swaroop A">A. Swaroop</name></author><author><name sortKey="Sowden, J C" uniqKey="Sowden J">J.C. Sowden</name></author><author><name sortKey="Ali, R R" uniqKey="Ali R">R.R. Ali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lakowski, J" uniqKey="Lakowski J">J. Lakowski</name></author><author><name sortKey="Baron, M" uniqKey="Baron M">M. Baron</name></author><author><name sortKey="Bainbridge, J" uniqKey="Bainbridge J">J. Bainbridge</name></author><author><name sortKey="Barber, A C" uniqKey="Barber A">A.C. Barber</name></author><author><name sortKey="Pearson, R A" uniqKey="Pearson R">R.A. Pearson</name></author><author><name sortKey="Ali, R R" uniqKey="Ali R">R.R. Ali</name></author><author><name sortKey="Sowden, J C" uniqKey="Sowden J">J.C. Sowden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, J W" uniqKey="Kim J">J.W. Kim</name></author><author><name sortKey="Yang, H J" uniqKey="Yang H">H.J. Yang</name></author><author><name sortKey="Oel, A P" uniqKey="Oel A">A.P. Oel</name></author><author><name sortKey="Brooks, M J" uniqKey="Brooks M">M.J. Brooks</name></author><author><name sortKey="Jia, L" uniqKey="Jia L">L. Jia</name></author><author><name sortKey="Plachetzki, D C" uniqKey="Plachetzki D">D.C. Plachetzki</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Allison, W T" uniqKey="Allison W">W.T. Allison</name></author><author><name sortKey="Swaroop, A" uniqKey="Swaroop A">A. Swaroop</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ueno, K" uniqKey="Ueno K">K. Ueno</name></author><author><name sortKey="Iwagawa, T" uniqKey="Iwagawa T">T. Iwagawa</name></author><author><name sortKey="Kuribayashi, H" uniqKey="Kuribayashi H">H. Kuribayashi</name></author><author><name sortKey="Baba, Y" uniqKey="Baba Y">Y. Baba</name></author><author><name sortKey="Nakauchi, H" uniqKey="Nakauchi H">H. Nakauchi</name></author><author><name sortKey="Murakami, A" uniqKey="Murakami A">A. Murakami</name></author><author><name sortKey="Nagasaki, M" uniqKey="Nagasaki M">M. Nagasaki</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y. Suzuki</name></author><author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S. Watanabe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Montana, C L" uniqKey="Montana C">C.L. Montana</name></author><author><name sortKey="Kolesnikov, A V" uniqKey="Kolesnikov A">A.V. Kolesnikov</name></author><author><name sortKey="Shen, S Q" uniqKey="Shen S">S.Q. Shen</name></author><author><name sortKey="Myers, C A" uniqKey="Myers C">C.A. Myers</name></author><author><name sortKey="Kefalov, V J" uniqKey="Kefalov V">V.J. Kefalov</name></author><author><name sortKey="Corbo, J C" uniqKey="Corbo J">J.C. Corbo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pearson, R A" uniqKey="Pearson R">R.A. Pearson</name></author><author><name sortKey="Gonzalez Cordero, A" uniqKey="Gonzalez Cordero A">A. Gonzalez-Cordero</name></author><author><name sortKey="West, E L" uniqKey="West E">E.L. West</name></author><author><name sortKey="Ribeiro, J R" uniqKey="Ribeiro J">J.R. Ribeiro</name></author><author><name sortKey="Aghaizu, N" uniqKey="Aghaizu N">N. Aghaizu</name></author><author><name sortKey="Goh, D" uniqKey="Goh D">D. Goh</name></author><author><name sortKey="Sampson, R D" uniqKey="Sampson R">R.D. Sampson</name></author><author><name sortKey="Georgiadis, A" uniqKey="Georgiadis A">A. Georgiadis</name></author><author><name sortKey="Waldron, P V" uniqKey="Waldron P">P.V. Waldron</name></author><author><name sortKey="Duran, Y" uniqKey="Duran Y">Y. Duran</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Santos Ferreira, T" uniqKey="Santos Ferreira T">T. Santos-Ferreira</name></author><author><name sortKey="Llonch, S" uniqKey="Llonch S">S. Llonch</name></author><author><name sortKey="Borsch, O" uniqKey="Borsch O">O. Borsch</name></author><author><name sortKey="Postel, K" uniqKey="Postel K">K. Postel</name></author><author><name sortKey="Haas, J" uniqKey="Haas J">J. Haas</name></author><author><name sortKey="Ader, M" uniqKey="Ader M">M. Ader</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pearson, R A" uniqKey="Pearson R">R.A. Pearson</name></author><author><name sortKey="Barber, A C" uniqKey="Barber A">A.C. Barber</name></author><author><name sortKey="West, E L" uniqKey="West E">E.L. West</name></author><author><name sortKey="Maclaren, R E" uniqKey="Maclaren R">R.E. MacLaren</name></author><author><name sortKey="Duran, Y" uniqKey="Duran Y">Y. Duran</name></author><author><name sortKey="Bainbridge, J W" uniqKey="Bainbridge J">J.W. Bainbridge</name></author><author><name sortKey="Sowden, J C" uniqKey="Sowden J">J.C. Sowden</name></author><author><name sortKey="Ali, R R" uniqKey="Ali R">R.R. Ali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tucker, B" uniqKey="Tucker B">B. Tucker</name></author><author><name sortKey="Klassen, H" uniqKey="Klassen H">H. Klassen</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L. Yang</name></author><author><name sortKey="Chen, D F" uniqKey="Chen D">D.F. Chen</name></author><author><name sortKey="Young, M J" uniqKey="Young M">M.J. Young</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, N" uniqKey="Wang N">N. Wang</name></author><author><name sortKey="Orr Urtreger, A" uniqKey="Orr Urtreger A">A. Orr-Urtreger</name></author><author><name sortKey="Korczyn, A D" uniqKey="Korczyn A">A.D. Korczyn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoglinger, G U" uniqKey="Hoglinger G">G.U. Höglinger</name></author><author><name sortKey="Rizk, P" uniqKey="Rizk P">P. Rizk</name></author><author><name sortKey="Muriel, M P" uniqKey="Muriel M">M.P. Muriel</name></author><author><name sortKey="Duyckaerts, C" uniqKey="Duyckaerts C">C. Duyckaerts</name></author><author><name sortKey="Oertel, W H" uniqKey="Oertel W">W.H. Oertel</name></author><author><name sortKey="Caille, I" uniqKey="Caille I">I. Caille</name></author><author><name sortKey="Hirsch, E C" uniqKey="Hirsch E">E.C. Hirsch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Santarelli, L" uniqKey="Santarelli L">L. Santarelli</name></author><author><name sortKey="Saxe, M" uniqKey="Saxe M">M. Saxe</name></author><author><name sortKey="Gross, C" uniqKey="Gross C">C. Gross</name></author><author><name sortKey="Surget, A" uniqKey="Surget A">A. Surget</name></author><author><name sortKey="Battaglia, F" uniqKey="Battaglia F">F. Battaglia</name></author><author><name sortKey="Dulawa, S" uniqKey="Dulawa S">S. Dulawa</name></author><author><name sortKey="Weisstaub, N" uniqKey="Weisstaub N">N. Weisstaub</name></author><author><name sortKey="Lee, J" uniqKey="Lee J">J. Lee</name></author><author><name sortKey="Duman, R" uniqKey="Duman R">R. Duman</name></author><author><name sortKey="Arancio, O" uniqKey="Arancio O">O. Arancio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cameron, H A" uniqKey="Cameron H">H.A. Cameron</name></author><author><name sortKey="Hazel, T G" uniqKey="Hazel T">T.G. Hazel</name></author><author><name sortKey="Mckay, R D" uniqKey="Mckay R">R.D. McKay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Santos Ferreira, T" uniqKey="Santos Ferreira T">T. Santos-Ferreira</name></author><author><name sortKey="Postel, K" uniqKey="Postel K">K. Postel</name></author><author><name sortKey="Stutzki, H" uniqKey="Stutzki H">H. Stutzki</name></author><author><name sortKey="Kurth, T" uniqKey="Kurth T">T. Kurth</name></author><author><name sortKey="Zeck, G" uniqKey="Zeck G">G. Zeck</name></author><author><name sortKey="Ader, M" uniqKey="Ader M">M. Ader</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Ther</journal-id><journal-id journal-id-type="iso-abbrev">Mol. Ther</journal-id><journal-title-group><journal-title>Molecular Therapy</journal-title></journal-title-group><issn pub-type="ppub">1525-0016</issn><issn pub-type="epub">1525-0024</issn><publisher><publisher-name>American Society of Gene & Cell Therapy</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28143742</article-id><article-id pub-id-type="pmc">5363218</article-id><article-id pub-id-type="publisher-id">S1525-0016(16)45497-3</article-id><article-id pub-id-type="doi">10.1016/j.ymthe.2016.12.015</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Cone Genesis Tracing by the <italic>Chrnb4</italic>-EGFP Mouse Line: Evidences of Cellular Material Fusion after Cone Precursor Transplantation</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Decembrini</surname><given-names>Sarah</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>Catherine</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Sennlaub</surname><given-names>Florian</given-names></name><xref rid="aff2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Chemtob</surname><given-names>Sylvain</given-names></name><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Biel</surname><given-names>Martin</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Samardzija</surname><given-names>Marijana</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Moulin</surname><given-names>Alexandre</given-names></name><xref rid="aff6" ref-type="aff">6</xref></contrib><contrib contrib-type="author"><name><surname>Behar-Cohen</surname><given-names>Francine</given-names></name><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Arsenijevic</surname><given-names>Yvan</given-names></name><email>yvan.arsenijevic@fa2.ch</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</aff><aff id="aff2"><label>2</label>Sorbonne Universités, UPMC/Univ Paris 06, UMRS 968, INSERM, U968, Institut de la Vision, 75012 Paris, France</aff><aff id="aff3"><label>3</label>Departments of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste. Justine Research Center, Montreal, QC H3T1C5, Canada</aff><aff id="aff4"><label>4</label>Center for Integrated Protein Science Munich CIPSM, Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 München, Germany</aff><aff id="aff5"><label>5</label>Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, 8952 Schlieren, Switzerland</aff><aff id="aff6"><label>6</label>Pathology Laboratory, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</aff><aff id="aff7"><label>7</label>Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author: Yvan Arsenijevic, Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland. <email>yvan.arsenijevic@fa2.ch</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>28</day><month>1</month><year>2017</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>01</day><month>3</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>28</day><month>1</month><year>2017</year></pub-date><volume>25</volume><issue>3</issue><fpage>634</fpage><lpage>653</lpage><history><date date-type="received"><day>30</day><month>4</month><year>2016</year></date><date date-type="accepted"><day>12</day><month>12</month><year>2016</year></date></history><permissions><copyright-statement>© 2017 The Author(s)</copyright-statement><copyright-year>2017</copyright-year><license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</license-p></license></permissions><abstract id="abs0010"><p>The cone function is essential to mediate high visual acuity, color vision, and daylight vision. Inherited cone dystrophies and age-related macular degeneration affect a substantial percentage of the world population. To identify and isolate the most competent cells for transplantation and integration into the retina, cone tracing during development would be an important added value. To that aim, the <italic>Chrnb4</italic>-EGFP mouse line was characterized throughout retinogenesis. It revealed a sub-population of early retinal progenitors expressing the reporter gene that is progressively restricted to mature cones during retina development. The presence of the native CHRNB4 protein was confirmed in EGFP-positive cells, and it presents a similar pattern in the human retina. Sub-retinal transplantations of distinct subpopulations of <italic>Chrnb4</italic>-EGFP-expressing cells revealed the embryonic day 15.5 high-EGFP population the most efficient cells to interact with host retinas to provoke the appearance of EGFP-positive cones in the photoreceptor layer. Importantly, transplantations into the DsRed retinas revealed material exchanges between donor and host retinas, as >80% of transplanted EGFP-positive cones also were DsRed positive. Whether this cell material fusion is of significant therapeutic advantage requires further thorough investigations. The <italic>Chrnb4</italic>-EGFP mouse line definitely opens new research perspectives in cone genesis and retina repair.</p></abstract><abstract abstract-type="teaser" id="abs0015"><p>In adult mouse and human retina, the beta-4 subunit of the Acetylcholine receptor (CHRNB4) is expressed only in cones. The <italic>Chrnb4</italic>-EGFP mouse served for cone lineage-tracing and transplantation studies. Transplantation of <italic>Chrnb4</italic>-EGFP cone precursors into DsRed retina revealed frequent bidirectional cellular material exchanges between donor and host cones.</p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>retina</kwd><kwd>transplantation</kwd><kwd>neurodegeneration</kwd><kwd>fusion</kwd><kwd>cones</kwd><kwd>retinal dystrophy</kwd></kwd-group></article-meta></front><floats-group><fig id="fig1"><label>Figure 1</label><caption><p>Progressive Restriction of <italic>Chrnb4</italic>-EGFP Expression in Developing Photoreceptors throughout Retinogenesis</p><p>(A–FII) Transversal sections of retinas at different developmental stages were collected from <italic>Chrnb4-</italic>EGFP reporter mice. (A–BII) EGFP detection is shown in round and elongated cells adjacent to the basal and to the most apical retinal region in E12 and E14 retinas. (B) White arrows indicate spindled cells in the central part of the retina expressing weak EGFP (probably progenitors). (C–CII) The EGFP expression is more restricted at the edge of the retinal apical side of E15.5 retinas. Few round cells at the basal retinal side still show EGFP expression (white arrows). (D–EII) In E18 and PN0 retinas, EGFP expression is exclusively restricted to the developing outer nuclear layer (dONL) in which photoreceptors differentiate. (F–FII) EGFP is expressed in a subset of photoreceptor cells at PN6, not in all photoreceptors. (F) The white arrow indicates the margin of the dONL. DAPI, nuclear staining (blue); Ba, basal; Ap, apical; PN, post-natal day; E, embryonic day. Scale bars, 20 μm.</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Investigation of the Chrnb4-EGFP-Positive Cell Proliferation during the Cone Generation Wave</p><p>Pregnant females were labeled for 24 hr with EdU at E12, E13, E15, or E17. (A–DII) Transversal sections are shown of retinas at E13, E14, E16, and E18 stained for EGPF and EdU. (A–D) Merged pictures show EGFP (green) and DAPI nuclear staining (in blue). (AI–DI) EdU labelings (red) at different developmental stages are shown. (AII–DII) Merged pictures show EdU-positive cells (red) and EGFP-positive cells (in green). Dashed lines delimit the apical (Ap) from the basal (Ba) retinal regions used for counting in (F) and (G). (E–G) Percentage of double EdU-/EGFP -positive cells were counted over the EGFP-positive cells detected in the whole (E), apical (F), and basal (G) retina. (H–J) Percentage of double Ki67- and EGFP-positive cells counted over the total number of EGFP-positive cells confirms the results achieved with the EdU labeling. DAPI, nuclear staining (blue); Ba, basal; Ap, apical. (E–G and J) ANOVA with Tukey’s correction, ***p < 0.001; n = 4. Error bars correspond to SEM. Scale bars, 25 μm (A–D, H, AI–DI, and HI) and 15 μm (AII–DII and HII).</p></caption><graphic xlink:href="gr2"></graphic></fig><fig id="fig3"><label>Figure 3</label><caption><p>EGFP Co-expression with the Post-mitotic Cone Marker RXRγ at E12</p><p>(A–CII) Transversal sections of E12 retinas from <italic>Chrnb4-</italic>EGFP reporter mice. (A–AII) OTX2, essential for photoreceptor differentiation, is detected in elongated EGFP-positive cells adjacent to the apical retinal region. (B–BII) Double RXRγ- EGFP-positive cones localized at both the apical and basal side of the retina. (C–CII) EGFP co-expression with PAX6-positive cells adjacent to the basal retinal region is shown. (A–C) Dashed lines delimit the Ap from the Ba retinal region used for counting in (D). (D) Percentage of double EGFP- RXRγ-positive cells were counted over the EGFP-positive cells detected in the whole, apical-central, and basal retina. Error bars correspond to SEM. (AII, BII, and CII) High-magnification pictures show the corresponding white squares. DAPI, nuclear staining (blue); Ba, basal; Ap, apical; n = 3. Scale bars, 50 μm (A–CI) and 15 μm (magnified insets).</p></caption><graphic xlink:href="gr3"></graphic></fig><fig id="fig4"><label>Figure 4</label><caption><p>E12-Derived EGFP-Positive Cells Generate Cones after Transplantation into Adult NOD/SCID Retinas</p><p>(A) Flow cytometry analysis of EGFP-positive cells from dissociated E12 mouse retinas. Different EGFP intensities and cell complexities were detected and gated in blue, green, and yellow, respectively. All EGFP-positive cells were injected. (B–E) Example is shown of rosette-like structures formed in the sub-retinal space of NOD/SCID mice, 4 weeks after grafting (white arrows in B). (C) PAX6-positive (in red) and EGFP-negative cells in the sub-retinal space of adult retinas are shown. (D) Transplanted cells resulted to be KI67 negative. (E–EII) Double GNAT2- EGFP-positive cone cells. (EI–II) High magnification of cell graft is shown (E, white square). DAPI, nuclear staining (blue); ONL and INL, outer and inner nuclear layer; n = 5. Scale bars, 30 μm (B–E) and 15 μm (EI–II).</p></caption><graphic xlink:href="gr4"></graphic></fig><fig id="fig5"><label>Figure 5</label><caption><p>EGFP Expression in Newly Born Post-mitotic RXRγ-Positive Cones of E15.5 Retinas</p><p>(A–CII) Transversal sections of E15.5 retinas from <italic>Chrnb4-</italic>EGFP mice. (A–AII) OTX2 detection is shown in EGFP-positive photoreceptors at the apical retinal side. (B–BII) Double RXRγ- EGFP-positive cones localized at both the apical and basal sides of the retina. (C–CII) EGFP co-expression with PAX6-positive cells adjacent to the basal retinal side is shown. (D) Percentage of double EGFP- RXRγ-positive cells was counted over the EGFP-positive cells detected in the whole, apical, and basal retina. (E) Percentage of RXRγ<sup>+</sup>-EGFP<sup>+</sup> was counted over the RXRγ-positive cells detected in the basal and apical-central retina. Error bars correspond to SEM. DAPI, nuclear staining (blue); Ba, basal; Ap, apical; n = 4. Scale bars, 20 μm (A–CII) and 8 μm (magnified pictures in insets).</p></caption><graphic xlink:href="gr5"></graphic></fig><fig id="fig6"><label>Figure 6</label><caption><p>Presumptive Cone Precursors and Newborn Cones from E15.5 <italic>Chrnb4</italic>-EGFP Retinas Generate the Appearance of EGFP-Positive Mature Cones after Transplantation into Adult NOD/SCID Retinas</p><p>(A) Flow cytometry analysis of <italic>Chrnb4</italic>-EGFP-positive cell populations from dissociated E15.5 mouse retinas. Only the cells presenting the highest EGFP expression (P5 gated cells, in green) were transplanted. (B and C) Examples show (B) mature and (C) immature cone photoreceptors detected in adult recipient retinas. Note the presence of outer segments (white arrow, B). (D) Example is shown of a 2-month-old <italic>Chrnb4</italic>-EGFP-positive mouse retina stained for GNAT2 as control staining. Mature GNAT2-positive (E) and GNAT1-negative cones (F) 4 weeks after transplantation into NOD/SCID mice are shown. (B, E, and F) White arrows indicate external segment or synapsis. (G) Quantification is shown of morphologically mature cells observed in the adult retinas defined by the presence of the external segment or synapsis-like morphology. DAPI, nuclear staining (blue); ONL and INL, outer and inner nuclear layer; ES, external segment; n = 4 per experiment. (D) No significant variations of cell integration were revealed with two different ages of mouse recipients, n = 3. Error bars correspond to SEM. Scale bars, 20 μm (B and C) and 5 μm (D–F insets).</p></caption><graphic xlink:href="gr6"></graphic></fig><fig id="fig7"><label>Figure 7</label><caption><p>Evidences of Donor and Host Cell Material Exchanges after the Transplantation of E15.5 Chrnb4-EGFP Cells into the Adult DsRed Retinas</p><p>(A–BV) Transversal sections of adult DsRed retinas transplanted with E15.5 <italic>Chrnb4-</italic>EGFP positive cells. (A–AV) An example is shown of a transplanted cell present in the host retina expressing only EGFP analyzed by the Manders’overlap coefficient visualized in the image as white spots. (B–BV) The same analyses were performed in a transplanted cell expressing EGFP and the host marker DsRed pointed out by the white arrow (BIV–V). (C–DI) Quantification of single- and double-labeled cells reveals that the large majority of EGFP-positive cells also express the host DsRed transgene reporter marker (C) and are dispersed in the ONL with a preference for the first two rows of photoreceptors (DI). EGFP-positive cells not containing DsRed are usually isolated (CI) and are also mainly located in the two first rows of photoreceptors of the outer part of the ONL (D). Error bars correspond to SEM. DAPI, nuclear staining (blue); ONL and INL, outer and inner nuclear layer; n = 6 injected mice. Scale bars, 15 μm (A–AII and B–BIII) and 5 μm (AIV and BIV–BV).</p></caption><graphic xlink:href="gr7"></graphic></fig><fig id="fig8"><label>Figure 8</label><caption><p><italic>Chrnb4</italic>-EGFP Is Expressed in All Cone Subtypes of Adult Mouse Retinas</p><p>(A–DII) Transversal sections of <italic>Chrnb4</italic>-EGFP mouse adult retinas. EGFP co-localization is shown with cone-specific proteins, such as GNAT2 (AII), RXRγ (BII), S-OPSIN (CII), and M/L-OPSIN (DII) (red labelings). The column AII–DII is a magnification of pictures from A to DI. ONL and INL, outer and inner nuclear layer; DAPI, nuclear staining (blue). Scale bars, 10 μm (A–D and AI–DI) and 20 μm (AII–CII).</p></caption><graphic xlink:href="gr8"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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