Inhibition and enhancement of reprogramming by chromatin modifying enzymes
Methods and compositions are provided for the production of stem cells and induced pluripotent stem cells, and for uses thereof.
1. A method of producing induced pluripotent stem cells, the method comprising
inhibiting Dot1L in a differentiated cell and culturing the differentiated cell under reprogramming conditions to produce induced pluripotent stem cells,
wherein the reprogramming conditions comprise a reprogramming cocktail comprising a transcription factor, and
wherein the reprogramming cocktail does not include Klf4 or c-Myc.
2. The method of claim 1 , wherein Dot1L is inhibited when the cell is cultured with the reprogramming cocktail.
3. The method of claim 1 , wherein the differentiated cell is a fibroblast.
4. The method of claim 1 , wherein inhibiting Dot1L comprises inhibiting the methyltransferase activity of Dot1L.
5. The method of claim 1 , wherein Dot1L is inhibited by contacting the differentiated cell with a composition comprising a compound of formula I, I, II, or IV.
6. The method of claim 1 , wherein Dot1L is inhibited by contacting the differentiated cell with a composition comprising a compound of formula:
7. The method of claim 1 , wherein Dot1L is inhibited by contacting the differentiated cell with an shRNA that knocks down Dot1L expression.
8. The method of claim 1 , wherein the reprogramming cocktail comprises Oct4 and Sox2.
9. The method of claim 1 , wherein the reprogramming cocktail consists essentially of Oct4 and Sox2.
10. A method of producing induced pluripotent stem cells, the method comprising
inhibiting SUV39H1 in a differentiated cell and culturing the differentiated cell under reprogramming conditions to produce induced pluripotent stem cells,
wherein the reprogramming conditions comprise a reprogramming cocktail that does not include Klf4 or c-Myc.