Document Detail

Mouse ES and iPS cells can form similar definitive endoderm despite differences in imprinted genes.
MedLine Citation:
PMID:  21537085     Owner:  NLM     Status:  MEDLINE    
The directed differentiation of iPS and ES cells into definitive endoderm (DE) would allow the derivation of otherwise inaccessible progenitors for endodermal tissues. However, a global comparison of the relative equivalency of DE derived from iPS and ES populations has not been performed. Recent reports of molecular differences between iPS and ES cells have raised uncertainty as to whether iPS cells could generate autologous endodermal lineages in vitro. Here, we show that both mouse iPS and parental ES cells exhibited highly similar in vitro capacity to undergo directed differentiation into DE progenitors. With few exceptions, both cell types displayed similar surges in gene expression of specific master transcriptional regulators and global transcriptomes that define the developmental milestones of DE differentiation. Microarray analysis showed considerable overlap between the genetic programs of DE derived from ES/iPS cells in vitro and authentic DE from mouse embryos in vivo. Intriguingly, iPS cells exhibited aberrant silencing of imprinted genes known to participate in endoderm differentiation, yet retained a robust ability to differentiate into DE. Our results show that, despite some molecular differences, iPS cells can be efficiently differentiated into DE precursors, reinforcing their potential for development of cell-based therapies for diseased endoderm-derived tissues.
Constantina Christodoulou; Tyler A Longmire; Steven S Shen; Alice Bourdon; Cesar A Sommer; Paul Gadue; Avrum Spira; Valerie Gouon-Evans; George J Murphy; Gustavo Mostoslavsky; Darrell N Kotton
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-05-02
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-02     Completed Date:  2011-08-17     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2313-25     Citation Subset:  AIM; IM    
Boston University Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
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MeSH Terms
Cell Differentiation / physiology
Cell Line / cytology,  metabolism
Cell Lineage
Cell Separation
Chromosome Mapping
Clone Cells / cytology,  metabolism
DNA Methylation
Embryonic Stem Cells / cytology*,  metabolism
Endoderm / cytology*
Fetal Proteins / biosynthesis,  genetics
Gene Expression Regulation, Developmental*
Genes, Reporter
Genomic Imprinting / physiology*
Induced Pluripotent Stem Cells / cytology*,  metabolism
Liver / embryology
Mice, SCID
Multipotent Stem Cells / cytology,  metabolism
Neoplasm Transplantation
Teratoma / pathology
Transcription Factors / biosynthesis,  genetics
Grant Support
1R01 HL095993-01/HL/NHLBI NIH HHS; 1RC2HL101535-01/HL/NHLBI NIH HHS; P01 HL047049-16A1/HL/NHLBI NIH HHS; UL1 RR025771/RR/NCRR NIH HHS
Reg. No./Substance:
0/Fetal Proteins; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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