Document Detail


Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation.
MedLine Citation:
PMID:  23293299     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Embryonic stem (ES) cells hold great promise with respect to their potential to be differentiated into desired cell types. Of interest are organs derived from the definitive endoderm, such as the pancreas and liver, and animal studies have revealed an essential role for Nodal in development of the definitive endoderm. Activin A is a related TGFβ member that acts through many of the same downstream signaling effectors as Nodal and is thought to mimic Nodal activity. Detailed characterization of ES cell-derived endodermal cell types by gene expression analysis in vitro and functional analysis in vivo reveal that, despite their similarity in gene expression, Nodal and Activin-derived endodermal cells exhibit a distinct difference in functional competence following transplantation into the developing mouse embryo. Pdx1-expressing cells arising from the respective endoderm populations exhibit extended differences in their competence to mature into insulin/c-peptide-expressing cells in vivo. Our findings underscore the importance of functional cell-type evaluation during stepwise differentiation of stem cells.
Authors:
Alice E Chen; Malgorzata Borowiak; Richard I Sherwood; Anastasie Kweudjeu; Douglas A Melton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  140     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-03-07     Revised Date:  2013-08-09    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  675-86     Citation Subset:  IM    
Affiliation:
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Culture Techniques / methods
Cell Differentiation
Cells, Cultured
Culture Media / metabolism
Embryo Culture Techniques
Embryo, Mammalian / cytology,  metabolism
Embryonic Stem Cells / cytology,  drug effects,  metabolism*
Endoderm / cytology*,  metabolism
Female
Fluorescent Antibody Technique
Gene Expression Profiling
Green Fluorescent Proteins / metabolism
HMGB Proteins / genetics,  metabolism
Humans
Inhibin-beta Subunits / metabolism,  pharmacology
Male
Mice
Mice, Inbred ICR
Nodal Protein / metabolism*,  pharmacology
Recombinant Proteins / metabolism,  pharmacology
SOXF Transcription Factors / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
//Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Culture Media; 0/HMGB Proteins; 0/Nodal Protein; 0/Nodal protein, mouse; 0/Recombinant Proteins; 0/SOXF Transcription Factors; 0/Sox17 protein, mouse; 0/inhibin beta A subunit; 147336-22-9/Green Fluorescent Proteins; 93443-12-0/Inhibin-beta Subunits
Comments/Corrections

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


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