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) contacting a population of human embryonic stem cells with Activin A to differentiate them into definitive endoderm cells, and
b) exposing the definitive endoderm cells of step a) to an effective amount of at least one compound listed in table 1 to increase the number of Pdx1 expressing cells in the differentiated cell population.
2. The method of claim 1 , in which the compound is compound 1 in table I.
3. The method of claim 2 , further comprising exposing the population of human embryonic stem cells to at least one additional agent.
4. The method of claim 3 , in which the at least one additional agent is FGF10.
5. A kit comprising:
human embryonic stem cells;
Activin A;
at least one compound listed in table 1; and
instructions for differentiating the stem cells to definitive endoderm using the Activin A and for using the at least one compound to increase the number of Pdx1 expressing cells in a differentiated cell population.
6. The kit of claim 5 , in which the compound is compound 1 in table 1.
7. The kit of claim 6 , further comprising at least one additional agent.
8. The kit of claim 7 , in which the at least one additional agent is FGF10.
9. A method of producing Pdx1+pancreatic precursors comprising:
a) contacting human embryonic stem cells with Activin A to produce definitive endoderm cells; and
b) contacting the definitive endoderm cells of with an effective amount of at least one compound listed in table 1 to increase the number and percentage of Pdx 1+pancreatic precursors.
10. The method of claim 9 , in which the at least one compound is compound 1 in table 1.
11. The method of claim 10 , further comprising differentiating the Pdx1+pancreatic precursors into mature pancreatic cells.