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
2011 Impact Factor: 36.28
2011 SCImago Journal Rankings: 7.767
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 Field
Value
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
2011 Impact Factor: 36.28
2011 SCImago Journal Rankings: 7.767
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
Author Affiliations
  1. Massachusetts General Hospital
  2. Harvard Stem Cell Institute