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Comparable Generation of Activin-Induced Definitive Endoderm via Additive Wnt or BMP Signaling in Absence of Serum by Teo, Adrian Kee Keong; Valdez, Ivan Achel; Dirice, Ercument; Kulkarni, Rohit N. is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Comparable Generation of Activin-Induced Definitive Endoderm via Additive Wnt or BMP Signaling in Absence of Serum about?

## Summary There is considerable interest in differentiating human pluripotent stem cells (hPSCs) into definitive endoderm (DE) and pancreatic cells for in vitro disease modeling and cell replacement therapy. Numerous protocols use fetal bovine serum, which contains poorly defined factors to induce DE formation. Here, we compared Wnt and BMP in their ability to cooperate with Activin signaling to promote DE formation in a chemically defined medium. Varying concentrations of WNT3A, glycogen synthase kinase (GSK)-3 inhibitors CHIR99021 and 6-bromoindirubin-3′-oxime (BIO), and BMP4 could independently co-operate with Activin to effectively induce DE formation even in the absence of serum. Overall, CHIR99021 is favored due to its cost effectiveness. Surprisingly, WNT3A was ineffective in suppressing E-CADHERIN/CDH1 and pluripotency factor gene expression unlike GSK-3 inhibitors or BMP4. Our findings indicate that both Wnt and BMP effectively synergize with Activin signaling to generate DE from hPSCs, although WNT3A requires additional factors to suppress the pluripotency program inherent in hPSCs.

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Author

Teo, Adrian Kee Keong; Valdez, Ivan Achel; Dirice, Ercument; Kulkarni, Rohit N.

Publisher

Elsevier ; Cell Press; Amsterdam: Elsevier; Elsevier BV (ISSN 2213-6711)

Published

2014

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)