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Article: Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages

TitleHuman ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
Authors
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 2009, v. 460 n. 7251, p. 113-117 How to Cite?
Abstract
The 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.
Persistent Identifierhttp://hdl.handle.net/10722/141708
ISSN
2013 Impact Factor: 42.351
ISI Accession Number ID
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.

References

 

Author Affiliations
  1. Massachusetts General Hospital
  2. Harvard Stem Cell Institute
DC FieldValueLanguage
dc.contributor.authorBu, Len_HK
dc.contributor.authorJiang, Xen_HK
dc.contributor.authorMartinPuig, Sen_HK
dc.contributor.authorCaron, Len_HK
dc.contributor.authorZhu, Sen_HK
dc.contributor.authorShao, Yen_HK
dc.contributor.authorRoberts, DJen_HK
dc.contributor.authorHuang, PLen_HK
dc.contributor.authorDomian, IJen_HK
dc.contributor.authorChien, KRen_HK
dc.date.accessioned2011-09-27T02:58:34Z-
dc.date.available2011-09-27T02:58:34Z-
dc.date.issued2009en_HK
dc.identifier.citationNature, 2009, v. 460 n. 7251, p. 113-117en_HK
dc.identifier.issn0028-0836en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141708-
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.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/natureen_HK
dc.relation.ispartofNatureen_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCell Divisionen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshCell Lineageen_HK
dc.subject.meshCoculture Techniquesen_HK
dc.subject.meshEmbryonic Stem Cells - cytology - metabolismen_HK
dc.subject.meshEndothelial Cells - cytologyen_HK
dc.subject.meshFetus - cytology - embryologyen_HK
dc.subject.meshHeart - embryologyen_HK
dc.subject.meshHomeodomain Proteins - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLIM-Homeodomain Proteinsen_HK
dc.subject.meshMultipotent Stem Cells - cytology - metabolismen_HK
dc.subject.meshMuscle, Smooth - cytologyen_HK
dc.subject.meshMyocardium - cytologyen_HK
dc.subject.meshMyocytes, Cardiac - cytologyen_HK
dc.subject.meshTranscription Factorsen_HK
dc.subject.meshWnt Proteins - metabolismen_HK
dc.subject.meshWnt3 Proteinen_HK
dc.titleHuman ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineagesen_HK
dc.typeArticleen_HK
dc.identifier.emailBu, L:leibu@hku.hken_HK
dc.identifier.authorityBu, L=rp01534en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/nature08191en_HK
dc.identifier.pmid19571884en_HK
dc.identifier.scopuseid_2-s2.0-67650071028en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67650071028&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume460en_HK
dc.identifier.issue7251en_HK
dc.identifier.spage113en_HK
dc.identifier.epage117en_HK
dc.identifier.eissn1476-4687-
dc.identifier.isiWOS:000267545200040-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridBu, L=8510445400en_HK
dc.identifier.scopusauthoridJiang, X=55187615600en_HK
dc.identifier.scopusauthoridMartinPuig, S=6508291981en_HK
dc.identifier.scopusauthoridCaron, L=7006626672en_HK
dc.identifier.scopusauthoridZhu, S=26868284800en_HK
dc.identifier.scopusauthoridShao, Y=54080435400en_HK
dc.identifier.scopusauthoridRoberts, DJ=35501850800en_HK
dc.identifier.scopusauthoridHuang, PL=7403659318en_HK
dc.identifier.scopusauthoridDomian, IJ=6602310746en_HK
dc.identifier.scopusauthoridChien, KR=35902336700en_HK
dc.identifier.citeulike5053350-

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