GENERATING DEFINITIVE ENDODERM AND PANCREATIC PROGENITOR CELLS

摘要

Compositions and methods of producing mammalian cell populations that include a high proportion of definitive endoderm cells, posterior foregut-like progenitor cells, pancreatic progenitor cells and/or pancreatic beta cells are described herein. Such cell populations are useful for treatment of diabetes.

主权项

1. A method comprising:
(a) contacting starting mammalian cells with a first composition comprising an effective amount of a TGFβ family member and a WNT activator, while the mammalian cells express pluripotency factors comprising OCT4, SOX2, and KLF4, wherein the effective amount is sufficient to generate a first cell population comprising definitive endoderm cells and wherein at least about 5% of the cells in the first population express Sox17 and/or Foxa2, but where the first cell population does not express detectable NANOG; and (b) contacting cells from the first cell population with a second composition comprising an effective amount of a TGFβ receptor inhibitor, a hedgehog pathway inhibitor, and a retinoic acid receptor agonist to generate a second cell population comprising pancreatic progenitor cells, wherein at least about 10% of the cells in the second population express Pdx1, Nkx6.1, Hnf6, or a combination thereof.