Cited by 386

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Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells

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Nostro, M. Cristina, Sarangi, Farida, Ogawa, Shinichiro, Holtzinger, Audrey, Corneo, Barbara, Li, Xueling, Micallef, Suzanne J., Park, In-Hyun, Basford, Christina, Wheeler, Michael B., Daley, George Q., Elefanty, Andrew G., Stanley, Edouard G., Keller, Gordon·2011·Development

DOI 10.1242/dev.055236

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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.

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See all 386

Authors: Nostro, M. C., Sarangi, F., Ogawa, S., Holtzinger, A., Corneo, B., Li, X., Micallef, S. J., Park, I.-H., Basford, C., Wheeler, M. B., Daley, G. Q., Elefanty, A. G., Stanley, E. G., & Keller, G.
Venue: Development
Publisher: The Company of Biologists
Published: 2011-03-01
Volume: 138
Issue: 5
Pages: 861-871
ISSN: 0950-1991 (ISSN-L)
1477-9129
DOI: 10.1242/dev.055236
OpenAlex: W2170781656
Cited by: 386
References: 63
FWCI: 16.22
Type: journal article
Language: en
Open access: green

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Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells

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