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Article: Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
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TitleHuman ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
 
AuthorsBu, L1 2
Jiang, X1 2
MartinPuig, S1 2
Caron, L1 2
Zhu, S1
Shao, Y1
Roberts, DJ1
Huang, PL1
Domian, IJ1 2
Chien, KR1 2
 
Issue Date2009
 
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
 
CitationNature, 2009, v. 460 n. 7251, p. 113-117 [How to Cite?]
DOI: http://dx.doi.org/10.1038/nature08191
 
AbstractThe generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential. Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart. In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1 + cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that purified ISL1 + primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine. © 2009 Macmillan Publishers Limited. All rights reserved.
 
ISSN0028-0836
2013 Impact Factor: 42.351
 
DOIhttp://dx.doi.org/10.1038/nature08191
 
ISI Accession Number IDWOS:000267545200040
Funding AgencyGrant Number
Foundation Alfonso Martin Escudero, Spain
Harvard Stem Cell Institute
Leducq Foundation
Funding Information:

We thank C. Cowan for advice on human ES cell culture and electroporation; A. Nagy for providing the DsRed-MST plasmid; Y. Qyang for discussion and comments; E. Hansson for a critical reading of this manuscript; M. Lindsay and M. Ortega-Molina for help on human fetal heart anatomy; L. B. Prickett-Rice and K. Folz-Donahue for flow cytometry support; and Advanced Bioscience Resources for providing the human fetal tissues. S. M. P. is funded by Foundation Alfonso Martin Escudero, Spain. This study is supported by Harvard Stem Cell Institute and the Leducq Foundation.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorBu, L
 
dc.contributor.authorJiang, X
 
dc.contributor.authorMartinPuig, S
 
dc.contributor.authorCaron, L
 
dc.contributor.authorZhu, S
 
dc.contributor.authorShao, Y
 
dc.contributor.authorRoberts, DJ
 
dc.contributor.authorHuang, PL
 
dc.contributor.authorDomian, IJ
 
dc.contributor.authorChien, KR
 
dc.date.accessioned2011-09-27T02:58:34Z
 
dc.date.available2011-09-27T02:58:34Z
 
dc.date.issued2009
 
dc.description.abstractThe generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential. Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart. In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1 + cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that purified ISL1 + primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine. © 2009 Macmillan Publishers Limited. All rights reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationNature, 2009, v. 460 n. 7251, p. 113-117 [How to Cite?]
DOI: http://dx.doi.org/10.1038/nature08191
 
dc.identifier.citeulike5053350
 
dc.identifier.doihttp://dx.doi.org/10.1038/nature08191
 
dc.identifier.eissn1476-4687
 
dc.identifier.epage117
 
dc.identifier.isiWOS:000267545200040
Funding AgencyGrant Number
Foundation Alfonso Martin Escudero, Spain
Harvard Stem Cell Institute
Leducq Foundation
Funding Information:

We thank C. Cowan for advice on human ES cell culture and electroporation; A. Nagy for providing the DsRed-MST plasmid; Y. Qyang for discussion and comments; E. Hansson for a critical reading of this manuscript; M. Lindsay and M. Ortega-Molina for help on human fetal heart anatomy; L. B. Prickett-Rice and K. Folz-Donahue for flow cytometry support; and Advanced Bioscience Resources for providing the human fetal tissues. S. M. P. is funded by Foundation Alfonso Martin Escudero, Spain. This study is supported by Harvard Stem Cell Institute and the Leducq Foundation.

 
dc.identifier.issn0028-0836
2013 Impact Factor: 42.351
 
dc.identifier.issue7251
 
dc.identifier.pmid19571884
 
dc.identifier.scopuseid_2-s2.0-67650071028
 
dc.identifier.spage113
 
dc.identifier.urihttp://hdl.handle.net/10722/141708
 
dc.identifier.volume460
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofNature
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshCell Differentiation
 
dc.subject.meshCell Division
 
dc.subject.meshCell Line
 
dc.subject.meshCell Lineage
 
dc.subject.meshCoculture Techniques
 
dc.subject.meshEmbryonic Stem Cells - cytology - metabolism
 
dc.subject.meshEndothelial Cells - cytology
 
dc.subject.meshFetus - cytology - embryology
 
dc.subject.meshHeart - embryology
 
dc.subject.meshHomeodomain Proteins - metabolism
 
dc.subject.meshHumans
 
dc.subject.meshLIM-Homeodomain Proteins
 
dc.subject.meshMultipotent Stem Cells - cytology - metabolism
 
dc.subject.meshMuscle, Smooth - cytology
 
dc.subject.meshMyocardium - cytology
 
dc.subject.meshMyocytes, Cardiac - cytology
 
dc.subject.meshTranscription Factors
 
dc.subject.meshWnt Proteins - metabolism
 
dc.subject.meshWnt3 Protein
 
dc.titleHuman ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
 
dc.typeArticle
 
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Author Affiliations
  1. Massachusetts General Hospital
  2. Harvard Stem Cell Institute