Compositions and methods for promoting the generation of PDX1+ pancreatic cells
Certain embodiments disclosed herein are directed to a method of producing pancreatic cells or pancreatic cell precursors by exposing human embryonic stem cells to an effective amount of at least one compound listed in Table I to differentiate the human embryonic stem cells into the pancreatic cells or the pancreatic cell precursors. Kits and pancreatic cell lines produced using the methods are also described.
1. A method of producing pancreatic Pdx1-expressing cells comprising:
a) exposing a population of human embryonic stem (hES) cells to an effective amount of at least one compound listed in Table 1 and a compound selected from the group consisting of FGF10, Wnt3α, Activin A, Activin B and KAAD-cyclopamine to differentiate the hES cells into definitive endoderm cells, and
b) obtaining a population of definitive endoderm cells which has increased expression of Pdx1 compared to a population of hES cells which were not exposed to a compound listed in Table 1.
2. A method of producing Pdx1-expressing pancreatic precursors comprising:
a) exposing a population of hES cells to an effective amount of at least one compound selected from the group consisting of FGF10, Wnt3α, Activin B and KAAD-cyclopamine to differentiate the hES cells into definitive endoderm cells, and
b) exposing the population of definitive endoderm cells to an effective amount of at least one compound listed in Table 1 to increase the percentage of Pdx-1 expressing precursors.
3. The method of claim 2 , in which the at least one compound is compound 1 in table 1.
4. The method of claim 3 , further comprising differentiating the Pdx1-expressing pancreatic precursors into mature pancreatic cells.