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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2011-2-9
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pubmed:abstractText |
The generation of insulin-producing ?-cells from human pluripotent stem cells is dependent on efficient endoderm induction and appropriate patterning and specification of this germ layer to a pancreatic fate. In this study, we elucidated the temporal requirements for TGF? family members and canonical WNT signaling at these developmental stages and show that the duration of nodal/activin A signaling plays a pivotal role in establishing an appropriate definitive endoderm population for specification to the pancreatic lineage. WNT signaling was found to induce a posterior endoderm fate and at optimal concentrations enhanced the development of pancreatic lineage cells. Inhibition of the BMP signaling pathway at specific stages was essential for the generation of insulin-expressing cells and the extent of BMP inhibition required varied widely among the cell lines tested. Optimal stage-specific manipulation of these pathways resulted in a striking 250-fold increase in the levels of insulin expression and yielded populations containing up to 25% C-peptide+ cells.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1477-9129
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pubmed:author |
pubmed-author:BasfordChristinaC,
pubmed-author:CorneoBarbaraB,
pubmed-author:DaleyGeorge QGQ,
pubmed-author:ElefantyAndrew GAG,
pubmed-author:HoltzingerAudreyA,
pubmed-author:KellerGordonG,
pubmed-author:LiXuelingX,
pubmed-author:MicallefSuzanne JSJ,
pubmed-author:NostroM CristinaMC,
pubmed-author:OgawaShinichiroS,
pubmed-author:ParkIn-HyunIH,
pubmed-author:SarangiFaridaF,
pubmed-author:StanleyEdouard GEG,
pubmed-author:WheelerMichael BMB
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pubmed:issnType |
Electronic
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pubmed:volume |
138
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
861-71
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21270052-Activins,
pubmed-meshheading:21270052-Body Patterning,
pubmed-meshheading:21270052-Bone Morphogenetic Proteins,
pubmed-meshheading:21270052-C-Peptide,
pubmed-meshheading:21270052-Cell Line,
pubmed-meshheading:21270052-Cell Lineage,
pubmed-meshheading:21270052-Endoderm,
pubmed-meshheading:21270052-Humans,
pubmed-meshheading:21270052-Insulin,
pubmed-meshheading:21270052-Insulin-Secreting Cells,
pubmed-meshheading:21270052-Pancreas,
pubmed-meshheading:21270052-Pluripotent Stem Cells,
pubmed-meshheading:21270052-Signal Transduction,
pubmed-meshheading:21270052-Transforming Growth Factor beta,
pubmed-meshheading:21270052-Wnt Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
Stage-specific signaling through TGF? family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells.
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pubmed:affiliation |
McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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