Programming human pluripotent stem cells into white and brown adipocytes
Identifieur interne : 000279 ( Main/Exploration ); précédent : 000278; suivant : 000280Programming human pluripotent stem cells into white and brown adipocytes
Auteurs : Tim Ahfeldt [États-Unis] ; Robert T. Schinzel [États-Unis, Allemagne] ; Youn-Kyoung Lee [États-Unis] ; David Hendrickson [États-Unis] ; Adam Kaplan [États-Unis] ; David H. Lum [États-Unis] ; Raymond Camahort [États-Unis] ; Fang Xia [États-Unis] ; Jennifer Shay [États-Unis] ; Eugene P. Rhee [États-Unis] ; Clary B. Clish [États-Unis] ; Rahul C. Deo [États-Unis] ; Tony Shen [États-Unis] ; Frank H. Lau [États-Unis] ; Alicia Cowley [États-Unis] ; Greg Mowrer [États-Unis] ; Heba Al-Siddiqi [États-Unis, Qatar] ; Matthias Nahrendorf [États-Unis] ; Kiran Musunuru [États-Unis] ; Robert E. Gerszten [États-Unis] ; John L. Rinn [États-Unis] ; Chad A. Cowan [États-Unis]Source :
- Nature Cell Biology [ 1465-7392 ] ; 2012-02.
Abstract
The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/orPRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 8590. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease.
Url:
DOI: 10.1038/ncb2411
Affiliations:
- Allemagne, Qatar, États-Unis
- Berlin, Massachusetts
- Berlin, Cambridge (Massachusetts)
- Université Harvard
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Rhee</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142</wicri:regionArea><wicri:noRegion>Massachusetts 02142</wicri:noRegion></affiliation></author><author><name sortKey="Clish, Clary B" sort="Clish, Clary B" uniqKey="Clish C" first="Clary B." last="Clish">Clary B. Clish</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142</wicri:regionArea><wicri:noRegion>Massachusetts 02142</wicri:noRegion></affiliation></author><author><name sortKey="Deo, Rahul C" sort="Deo, Rahul C" uniqKey="Deo R" first="Rahul C." last="Deo">Rahul C. Deo</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143</wicri:regionArea><wicri:noRegion>California 94143</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of California San Francisco, San Francisco, California 94143</wicri:regionArea><wicri:noRegion>California 94143</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Human Genetics, University of California San Francisco,San Francisco, California 94143</wicri:regionArea><wicri:noRegion>California 94143</wicri:noRegion></affiliation></author><author><name sortKey="Shen, Tony" sort="Shen, Tony" uniqKey="Shen T" first="Tony" last="Shen">Tony Shen</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138</wicri:regionArea><orgName type="university">Université Harvard</orgName><placeName><settlement type="city">Cambridge (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation></author><author><name sortKey="Lau, Frank H" sort="Lau, Frank H" uniqKey="Lau F" first="Frank H." last="Lau">Frank H. Lau</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation></author><author><name sortKey="Cowley, Alicia" sort="Cowley, Alicia" uniqKey="Cowley A" first="Alicia" last="Cowley">Alicia Cowley</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138</wicri:regionArea><orgName type="university">Université Harvard</orgName><placeName><settlement type="city">Cambridge (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation></author><author><name sortKey="Mowrer, Greg" sort="Mowrer, Greg" uniqKey="Mowrer G" first="Greg" last="Mowrer">Greg Mowrer</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation></author><author><name sortKey="Al Siddiqi, Heba" sort="Al Siddiqi, Heba" uniqKey="Al Siddiqi H" first="Heba" last="Al-Siddiqi">Heba Al-Siddiqi</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138</wicri:regionArea><orgName type="university">Université Harvard</orgName><placeName><settlement type="city">Cambridge (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Qatar</country><wicri:regionArea>Research Division, Qatar Foundation,Doha</wicri:regionArea><wicri:noRegion>Doha</wicri:noRegion></affiliation></author><author><name sortKey="Nahrendorf, Matthias" sort="Nahrendorf, Matthias" uniqKey="Nahrendorf M" first="Matthias" last="Nahrendorf">Matthias Nahrendorf</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge St.,Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation></author><author><name sortKey="Musunuru, Kiran" sort="Musunuru, Kiran" uniqKey="Musunuru K" first="Kiran" last="Musunuru">Kiran Musunuru</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138</wicri:regionArea><orgName type="university">Université Harvard</orgName><placeName><settlement type="city">Cambridge (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142</wicri:regionArea><wicri:noRegion>Massachusetts 02142</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Brigham and Womens Hospital, Boston, Massachusetts 02115</wicri:regionArea><wicri:noRegion>Massachusetts 02115</wicri:noRegion></affiliation></author><author><name sortKey="Gerszten, Robert E" sort="Gerszten, Robert E" uniqKey="Gerszten R" first="Robert E." last="Gerszten">Robert E. Gerszten</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142</wicri:regionArea><wicri:noRegion>Massachusetts 02142</wicri:noRegion></affiliation></author><author><name sortKey="Rinn, John L" sort="Rinn, John L" uniqKey="Rinn J" first="John L." last="Rinn">John L. Rinn</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138</wicri:regionArea><orgName type="university">Université Harvard</orgName><placeName><settlement type="city">Cambridge (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142</wicri:regionArea><wicri:noRegion>Massachusetts 02142</wicri:noRegion></affiliation></author><author><name sortKey="Cowan, Chad A" sort="Cowan, Chad A" uniqKey="Cowan C" first="Chad A." last="Cowan">Chad A. Cowan</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138</wicri:regionArea><orgName type="university">Université Harvard</orgName><placeName><settlement type="city">Cambridge (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114</wicri:regionArea><wicri:noRegion>Massachusetts 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142</wicri:regionArea><wicri:noRegion>Massachusetts 02142</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Nature Cell Biology</title><idno type="ISSN">1465-7392</idno><idno type="eISSN">1476-4679</idno><imprint><publisher>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</publisher><date type="published" when="2012-02">2012-02</date><biblScope unit="volume">14</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="209">209</biblScope><biblScope unit="page" to="219">219</biblScope></imprint><idno type="ISSN">1465-7392</idno></series><idno type="istex">4CE3AA353259899142A7F08B8BCB3A4C28A9F4EE</idno><idno type="DOI">10.1038/ncb2411</idno><idno type="ArticleID">ncb2411</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1465-7392</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/orPRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 8590. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Qatar</li><li>États-Unis</li></country><region><li>Berlin</li><li>Massachusetts</li></region><settlement><li>Berlin</li><li>Cambridge (Massachusetts)</li></settlement><orgName><li>Université Harvard</li></orgName></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Ahfeldt, Tim" sort="Ahfeldt, Tim" uniqKey="Ahfeldt T" first="Tim" last="Ahfeldt">Tim Ahfeldt</name></region><name sortKey="Ahfeldt, Tim" sort="Ahfeldt, Tim" uniqKey="Ahfeldt T" first="Tim" last="Ahfeldt">Tim Ahfeldt</name><name sortKey="Ahfeldt, Tim" sort="Ahfeldt, Tim" uniqKey="Ahfeldt T" first="Tim" last="Ahfeldt">Tim Ahfeldt</name><name sortKey="Al Siddiqi, Heba" sort="Al Siddiqi, Heba" uniqKey="Al Siddiqi H" first="Heba" last="Al-Siddiqi">Heba Al-Siddiqi</name><name sortKey="Al Siddiqi, Heba" sort="Al Siddiqi, Heba" uniqKey="Al Siddiqi H" first="Heba" last="Al-Siddiqi">Heba Al-Siddiqi</name><name sortKey="Al Siddiqi, Heba" sort="Al Siddiqi, Heba" uniqKey="Al Siddiqi H" first="Heba" last="Al-Siddiqi">Heba Al-Siddiqi</name><name sortKey="Camahort, Raymond" sort="Camahort, Raymond" uniqKey="Camahort R" first="Raymond" last="Camahort">Raymond Camahort</name><name sortKey="Camahort, Raymond" sort="Camahort, Raymond" uniqKey="Camahort R" first="Raymond" last="Camahort">Raymond Camahort</name><name sortKey="Camahort, Raymond" sort="Camahort, Raymond" uniqKey="Camahort R" first="Raymond" last="Camahort">Raymond Camahort</name><name sortKey="Clish, Clary B" sort="Clish, Clary B" uniqKey="Clish C" first="Clary B." last="Clish">Clary B. Clish</name><name sortKey="Cowan, Chad A" sort="Cowan, Chad A" uniqKey="Cowan C" first="Chad A." last="Cowan">Chad A. Cowan</name><name sortKey="Cowan, Chad A" sort="Cowan, Chad A" uniqKey="Cowan C" first="Chad A." last="Cowan">Chad A. Cowan</name><name sortKey="Cowan, Chad A" sort="Cowan, Chad A" uniqKey="Cowan C" first="Chad A." last="Cowan">Chad A. Cowan</name><name sortKey="Cowan, Chad A" sort="Cowan, Chad A" uniqKey="Cowan C" first="Chad A." last="Cowan">Chad A. Cowan</name><name sortKey="Cowan, Chad A" sort="Cowan, Chad A" uniqKey="Cowan C" first="Chad A." last="Cowan">Chad A. Cowan</name><name sortKey="Cowley, Alicia" sort="Cowley, Alicia" uniqKey="Cowley A" first="Alicia" last="Cowley">Alicia Cowley</name><name sortKey="Cowley, Alicia" sort="Cowley, Alicia" uniqKey="Cowley A" first="Alicia" last="Cowley">Alicia Cowley</name><name sortKey="Deo, Rahul C" sort="Deo, Rahul C" uniqKey="Deo R" first="Rahul C." last="Deo">Rahul C. Deo</name><name sortKey="Deo, Rahul C" sort="Deo, Rahul C" uniqKey="Deo R" first="Rahul C." last="Deo">Rahul C. Deo</name><name sortKey="Deo, Rahul C" sort="Deo, Rahul C" uniqKey="Deo R" first="Rahul C." last="Deo">Rahul C. Deo</name><name sortKey="Gerszten, Robert E" sort="Gerszten, Robert E" uniqKey="Gerszten R" first="Robert E." last="Gerszten">Robert E. Gerszten</name><name sortKey="Gerszten, Robert E" sort="Gerszten, Robert E" uniqKey="Gerszten R" first="Robert E." last="Gerszten">Robert E. Gerszten</name><name sortKey="Hendrickson, David" sort="Hendrickson, David" uniqKey="Hendrickson D" first="David" last="Hendrickson">David Hendrickson</name><name sortKey="Hendrickson, David" sort="Hendrickson, David" uniqKey="Hendrickson D" first="David" last="Hendrickson">David Hendrickson</name><name sortKey="Kaplan, Adam" sort="Kaplan, Adam" uniqKey="Kaplan A" first="Adam" last="Kaplan">Adam Kaplan</name><name sortKey="Kaplan, Adam" sort="Kaplan, Adam" uniqKey="Kaplan A" first="Adam" last="Kaplan">Adam Kaplan</name><name sortKey="Kaplan, Adam" sort="Kaplan, Adam" uniqKey="Kaplan A" first="Adam" last="Kaplan">Adam Kaplan</name><name sortKey="Lau, Frank H" sort="Lau, Frank H" uniqKey="Lau F" first="Frank H." last="Lau">Frank H. Lau</name><name sortKey="Lau, Frank H" sort="Lau, Frank H" uniqKey="Lau F" first="Frank H." last="Lau">Frank H. Lau</name><name sortKey="Lee, Youn Kyoung" sort="Lee, Youn Kyoung" uniqKey="Lee Y" first="Youn-Kyoung" last="Lee">Youn-Kyoung Lee</name><name sortKey="Lee, Youn Kyoung" sort="Lee, Youn Kyoung" uniqKey="Lee Y" first="Youn-Kyoung" last="Lee">Youn-Kyoung Lee</name><name sortKey="Lee, Youn Kyoung" sort="Lee, Youn Kyoung" uniqKey="Lee Y" first="Youn-Kyoung" last="Lee">Youn-Kyoung Lee</name><name sortKey="Lum, David H" sort="Lum, David H" uniqKey="Lum D" first="David H." last="Lum">David H. Lum</name><name sortKey="Lum, David H" sort="Lum, David H" uniqKey="Lum D" first="David H." last="Lum">David H. Lum</name><name sortKey="Mowrer, Greg" sort="Mowrer, Greg" uniqKey="Mowrer G" first="Greg" last="Mowrer">Greg Mowrer</name><name sortKey="Mowrer, Greg" sort="Mowrer, Greg" uniqKey="Mowrer G" first="Greg" last="Mowrer">Greg Mowrer</name><name sortKey="Musunuru, Kiran" sort="Musunuru, Kiran" uniqKey="Musunuru K" first="Kiran" last="Musunuru">Kiran Musunuru</name><name sortKey="Musunuru, Kiran" sort="Musunuru, Kiran" uniqKey="Musunuru K" first="Kiran" last="Musunuru">Kiran Musunuru</name><name sortKey="Musunuru, Kiran" sort="Musunuru, Kiran" uniqKey="Musunuru K" first="Kiran" last="Musunuru">Kiran Musunuru</name><name sortKey="Nahrendorf, Matthias" sort="Nahrendorf, Matthias" uniqKey="Nahrendorf M" first="Matthias" last="Nahrendorf">Matthias Nahrendorf</name><name sortKey="Rhee, Eugene P" sort="Rhee, Eugene P" uniqKey="Rhee E" first="Eugene P." last="Rhee">Eugene P. Rhee</name><name sortKey="Rhee, Eugene P" sort="Rhee, Eugene P" uniqKey="Rhee E" first="Eugene P." last="Rhee">Eugene P. Rhee</name><name sortKey="Rinn, John L" sort="Rinn, John L" uniqKey="Rinn J" first="John L." last="Rinn">John L. Rinn</name><name sortKey="Rinn, John L" sort="Rinn, John L" uniqKey="Rinn J" first="John L." last="Rinn">John L. Rinn</name><name sortKey="Schinzel, Robert T" sort="Schinzel, Robert T" uniqKey="Schinzel R" first="Robert T." last="Schinzel">Robert T. Schinzel</name><name sortKey="Schinzel, Robert T" sort="Schinzel, Robert T" uniqKey="Schinzel R" first="Robert T." last="Schinzel">Robert T. Schinzel</name><name sortKey="Schinzel, Robert T" sort="Schinzel, Robert T" uniqKey="Schinzel R" first="Robert T." last="Schinzel">Robert T. Schinzel</name><name sortKey="Shay, Jennifer" sort="Shay, Jennifer" uniqKey="Shay J" first="Jennifer" last="Shay">Jennifer Shay</name><name sortKey="Shay, Jennifer" sort="Shay, Jennifer" uniqKey="Shay J" first="Jennifer" last="Shay">Jennifer Shay</name><name sortKey="Shay, Jennifer" sort="Shay, Jennifer" uniqKey="Shay J" first="Jennifer" last="Shay">Jennifer Shay</name><name sortKey="Shen, Tony" sort="Shen, Tony" uniqKey="Shen T" first="Tony" last="Shen">Tony Shen</name><name sortKey="Shen, Tony" sort="Shen, Tony" uniqKey="Shen T" first="Tony" last="Shen">Tony Shen</name><name sortKey="Xia, Fang" sort="Xia, Fang" uniqKey="Xia F" first="Fang" last="Xia">Fang Xia</name><name sortKey="Xia, Fang" sort="Xia, Fang" uniqKey="Xia F" first="Fang" last="Xia">Fang Xia</name><name sortKey="Xia, Fang" sort="Xia, Fang" uniqKey="Xia F" first="Fang" last="Xia">Fang Xia</name></country><country name="Allemagne"><region name="Berlin"><name sortKey="Schinzel, Robert T" sort="Schinzel, Robert T" uniqKey="Schinzel R" first="Robert T." last="Schinzel">Robert T. Schinzel</name></region></country><country name="Qatar"><noRegion><name sortKey="Al Siddiqi, Heba" sort="Al Siddiqi, Heba" uniqKey="Al Siddiqi H" first="Heba" last="Al-Siddiqi">Heba Al-Siddiqi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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