| Literature DB >> 21270052 |
M Cristina Nostro1, Farida Sarangi, Shinichiro Ogawa, Audrey Holtzinger, Barbara Corneo, Xueling Li, Suzanne J Micallef, In-Hyun Park, Christina Basford, Michael B Wheeler, George Q Daley, Andrew G Elefanty, Edouard G Stanley, Gordon Keller.
Abstract
The generation of insulin-producing β-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 TGFβ 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.Entities:
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Year: 2011 PMID： 21270052 PMCID： PMC3035090 DOI： 10.1242/dev.055236
Source DB: PubMed Journal: Development ISSN： 0950-1991 Impact factor: 6.868