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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>In Vitro</italic> and <italic>in Vivo</italic> Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-X<sub>L</sub><xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Courtois, Elise T" sort="Courtois, Elise T" uniqKey="Courtois E" first="Elise T." last="Courtois">Elise T. Courtois</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Castillo, Claudia G" sort="Castillo, Claudia G" uniqKey="Castillo C" first="Claudia G." last="Castillo">Claudia G. Castillo</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Seiz, Emma G" sort="Seiz, Emma G" uniqKey="Seiz E" first="Emma G." last="Seiz">Emma G. Seiz</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ramos, Milagros" sort="Ramos, Milagros" uniqKey="Ramos M" first="Milagros" last="Ramos">Milagros Ramos</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Bueno, Carlos" sort="Bueno, Carlos" uniqKey="Bueno C" first="Carlos" last="Bueno">Carlos Bueno</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Liste, Isabel" sort="Liste, Isabel" uniqKey="Liste I" first="Isabel" last="Liste">Isabel Liste</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Martinez Serrano, Alberto" sort="Martinez Serrano, Alberto" uniqKey="Martinez Serrano A" first="Alberto" last="Martínez-Serrano">Alberto Martínez-Serrano</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20106970</idno><idno type="pmc">2843236</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843236</idno><idno type="RBID">PMC:2843236</idno><idno type="doi">10.1074/jbc.M109.054312</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000227</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000227</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>In Vitro</italic> and <italic>in Vivo</italic> Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-X<sub>L</sub><xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Courtois, Elise T" sort="Courtois, Elise T" uniqKey="Courtois E" first="Elise T." last="Courtois">Elise T. Courtois</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Castillo, Claudia G" sort="Castillo, Claudia G" uniqKey="Castillo C" first="Claudia G." last="Castillo">Claudia G. Castillo</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Seiz, Emma G" sort="Seiz, Emma G" uniqKey="Seiz E" first="Emma G." last="Seiz">Emma G. Seiz</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ramos, Milagros" sort="Ramos, Milagros" uniqKey="Ramos M" first="Milagros" last="Ramos">Milagros Ramos</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Bueno, Carlos" sort="Bueno, Carlos" uniqKey="Bueno C" first="Carlos" last="Bueno">Carlos Bueno</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Liste, Isabel" sort="Liste, Isabel" uniqKey="Liste I" first="Isabel" last="Liste">Isabel Liste</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Martinez Serrano, Alberto" sort="Martinez Serrano, Alberto" uniqKey="Martinez Serrano A" first="Alberto" last="Martínez-Serrano">Alberto Martínez-Serrano</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Human neural stem cells derived from the ventral mesencephalon (VM) are powerful research tools and candidates for cell therapies in Parkinson disease. Previous studies with VM dopaminergic neuron (DAn) precursors indicated poor growth potential and unstable phenotypical properties. Using the model cell line hVM1 (human ventral mesencephalic neural stem cell line 1; a new human fetal VM stem cell line), we have found that Bcl-X<sub>L</sub> enhances the generation of DAn from VM human neural stem cells. Mechanistically, Bcl-X<sub>L</sub> not only exerts the expected antiapoptotic effect but also induces proneural (<italic>NGN2</italic> and <italic>NEUROD1</italic>) and dopamine-related transcription factors, resulting in a high yield of DAn with the correct phenotype of substantia nigra pars compacta (SNpc). The expression of key genes directly involved in VM/SNpc dopaminergic patterning, differentiation, and maturation (<italic>EN1</italic>, <italic>LMX1B</italic>, <italic>PITX3</italic>, <italic>NURR1</italic>, <italic>VMAT2</italic>, <italic>GIRK2</italic>, and dopamine transporter) is thus enhanced by Bcl-X<sub>L</sub>. These effects on neurogenesis occur in parallel to a decrease in glia generation. These <italic>in vitro</italic> Bcl-X<sub>L</sub> effects are paralleled in <italic>vivo</italic>, after transplantation in hemiparkinsonian rats, where hVM1-Bcl-X<sub>L</sub> cells survive, integrate, and differentiate into DAn, alleviating behavioral motor asymmetry. Bcl-X<sub>L</sub> then allows for human fetal VM stem cells to stably generate mature SNpc DAn both <italic>in vitro</italic> and <italic>in vivo</italic> and is thus proposed as a helpful factor for the development of cell therapies for neurodegenerative conditions, Parkinson disease in particular.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Biol Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20106970</article-id><article-id pub-id-type="pmc">2843236</article-id><article-id pub-id-type="publisher-id">M109.054312</article-id><article-id pub-id-type="doi">10.1074/jbc.M109.054312</article-id><article-categories><subj-group subj-group-type="heading"><subject>Neurobiology</subject></subj-group></article-categories><title-group><article-title><italic>In Vitro</italic> and <italic>in Vivo</italic> Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-X<sub>L</sub><xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Courtois</surname><given-names>Elise T.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Castillo</surname><given-names>Claudia G.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff3"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Seiz</surname><given-names>Emma G.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ramos</surname><given-names>Milagros</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bueno</surname><given-names>Carlos</given-names></name><xref ref-type="aff" rid="aff2"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liste</surname><given-names>Isabel</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Martínez-Serrano</surname><given-names>Alberto</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Center of Molecular Biology Severo Ochoa (Consejo Superior de Investigaciones Científicas-UAM), Department of Molecular Biology, Autonomous University of Madrid, 28049 Madrid, Spain,</aff><aff id="aff2">the<label>¶</label>Institute of Neurosciences, University Miguel Hernandez of Elche, 03550 Alicante, Spain, and</aff><aff id="aff3">the<label>§</label>Department of Biochemistry, Faculty of Medicine, University of San Luis Potosí, 782 San Luis Potosí, México</aff></contrib-group><author-notes><corresp id="cor1"><label>1</label> To whom correspondence should be addressed: <addr-line>Center of Molecular Biology Severo Ochoa, C/ Nicolas Cabrera 1, 28049 Madrid, Spain.</addr-line> Tel.: <phone>34-91-196-4620</phone>; Fax: <fax>34-91-196-4420</fax>; E-mail:<email>amserrano@cbm.uam.es</email>.</corresp></author-notes><pub-date pub-type="ppub"><day>26</day><month>3</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>27</day><month>1</month><year>2010</year></pub-date><volume>285</volume><issue>13</issue><fpage>9881</fpage><lpage>9897</lpage><history><date date-type="received"><day>10</day><month>8</month><year>2009</year></date><date date-type="rev-recd"><day>15</day><month>1</month><year>2010</year></date></history><permissions><copyright-statement>© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc01310009881.pdf"></self-uri><abstract><p>Human neural stem cells derived from the ventral mesencephalon (VM) are powerful research tools and candidates for cell therapies in Parkinson disease. Previous studies with VM dopaminergic neuron (DAn) precursors indicated poor growth potential and unstable phenotypical properties. Using the model cell line hVM1 (human ventral mesencephalic neural stem cell line 1; a new human fetal VM stem cell line), we have found that Bcl-X<sub>L</sub> enhances the generation of DAn from VM human neural stem cells. Mechanistically, Bcl-X<sub>L</sub> not only exerts the expected antiapoptotic effect but also induces proneural (<italic>NGN2</italic> and <italic>NEUROD1</italic>) and dopamine-related transcription factors, resulting in a high yield of DAn with the correct phenotype of substantia nigra pars compacta (SNpc). The expression of key genes directly involved in VM/SNpc dopaminergic patterning, differentiation, and maturation (<italic>EN1</italic>, <italic>LMX1B</italic>, <italic>PITX3</italic>, <italic>NURR1</italic>, <italic>VMAT2</italic>, <italic>GIRK2</italic>, and dopamine transporter) is thus enhanced by Bcl-X<sub>L</sub>. These effects on neurogenesis occur in parallel to a decrease in glia generation. These <italic>in vitro</italic> Bcl-X<sub>L</sub> effects are paralleled in <italic>vivo</italic>, after transplantation in hemiparkinsonian rats, where hVM1-Bcl-X<sub>L</sub> cells survive, integrate, and differentiate into DAn, alleviating behavioral motor asymmetry. Bcl-X<sub>L</sub> then allows for human fetal VM stem cells to stably generate mature SNpc DAn both <italic>in vitro</italic> and <italic>in vivo</italic> and is thus proposed as a helpful factor for the development of cell therapies for neurodegenerative conditions, Parkinson disease in particular.</p></abstract><kwd-group><kwd>Cell Death</kwd><kwd>Neural Stem Cell</kwd><kwd>Neurodifferentiation</kwd><kwd>Neuroprogenitor Cell</kwd><kwd>Parkinson Disease</kwd><kwd>Dopamine</kwd><kwd>Dopaminergic Neurons</kwd><kwd>Hemiparkinsonian Model</kwd><kwd>Neural Transplantation</kwd><kwd>Ventral Mesencephalon</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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