Inhibition and enhancement of reprogramming by chromatin modifying enzymes

Abstract

In one aspect, the disclosure provides methods and compositions for the production of stem cells. In one aspect, the disclosure provides methods and uses of stem cells. In some embodiments, the stem cells are induced pluripotent stem cells.

What is claimed is: 
     
         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.   
     
     
         2 . The method of  claim 1 , wherein inhibiting Dot1L comprises inhibiting the methyltransferase activity of Dot1L. 
     
     
         3 . The method of  claim 1 , wherein Dot1L is inhibited by contacting the differentiated cell with a composition comprising a compound of formula I, II, III, or IV. 
     
     
         4 . The method of  claim 1 , wherein Dot1L is inhibited by contacting the differentiated cell with a composition comprising a compound of formula: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 1 , wherein Dot1L is inhibited by contacting the differentiated cell with an shRNA that knocks down Dot1L expression. 
     
     
         6 . The method of  claim 1 , wherein the reprogramming conditions comprise a reprogramming cocktail comprising a transcription factor. 
     
     
         7 . The method of  claim 6 , wherein the reprogramming cocktail comprises Oct4 and Sox2. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 6 , wherein the reprogramming cocktail does not include Klf4 or c-Myc. 
     
     
         10 . The method of  claim 6 , wherein Dot1L is inhibited when the cell is cultured with the reprogramming cocktail. 
     
     
         11 . The method of  claim 1 , wherein the differentiated cell is a fibroblast. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the differentiated cell is a human cell. 
     
     
         14 . The method of  claim 13 , wherein the differentiated human cell is dH1fs, IMR-90 or MRC-5. 
     
     
         15 . The method of  claim 1 , wherein the differentiated cell is a mouse cell. 
     
     
         16 - 19 . (canceled) 
     
     
         20 . A method of accelerating the production of induced pluripotent stem cells, the method comprising
 inhibiting Dot1L in a differentiated cell and culturing the differentiated cell under reprogramming conditions to accelerate the production of induced pluripotent stem cells, wherein the production of induced pluripotent stem cells is accelerated compared to a differentiated cell in which Dot1L is not inhibited.   
     
     
         21 . A method of producing induced pluripotent stem cells, the method comprising
 upregulating the expression of Nanog and Lin28 in a differentiated cell and culturing the differentiated cell under reprogramming conditions to produce induced pluripotent stem cells.   
     
     
         22 . The method of  claim 21 , wherein the expression of Nanog and Lin28 is upregulated by inhibiting Dot1L. 
     
     
         23 . 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.   
     
     
         24 . A method of producing induced pluripotent stem cells, the method comprising
 inhibiting YY1 in a differentiated cell and culturing the differentiated cell under reprogramming conditions to produce induced pluripotent stem cells.   
     
     
         25 . A composition comprising
 a population of human induced pluripotent stem cells produced according to the method of  claim 1 .   
     
     
         26 . (canceled) 
     
     
         27 . A method of treatment comprising administering to a person in need thereof the composition of  claim 25 . 
     
     
         28 . (canceled)