Modulating cell proliferation and pluripotency

Abstract

Disclosed herein are compositions, systems, and methods for modulating proliferation, differentiation and pluripotency of cells.

1 - 26 . (canceled) 
     
     
         27 . A cell culture comprising a population of stem cells or progenitor cells and a medium, wherein the medium comprises an α-ketoglutarate compound, a mitogen activated protein kinase (MAPK) inhibitor, and a glycogen synthase kinase 3β (GSK3β) inhibitor. 
     
     
         28 - 45 . (canceled) 
     
     
         46 . The cell culture of  claim 27 , wherein the α-ketoglutarate compound is cell permeable. 
     
     
         47 . The cell culture of  claim 46 , wherein the α-ketoglutarate compound is dimethyl α-ketoglutarate (DM-αKG). 
     
     
         48 . The cell culture of  claim 27 , wherein the stem cells are embryonic stem cells or adult stem cells. 
     
     
         49 . The cell culture of  claim 27 , wherein the progenitor cells are induced pluripotent stem cells. 
     
     
         50 . The cell culture of  claim 27 , wherein the MAPK inhibitor is a MEK inhibitor, an Erk inhibitor, or a p38 inhibitor. 
     
     
         51 . The cell culture of  claim 27 , wherein no exogenous glutamine is present in the medium. 
     
     
         52 . The cell culture of  claim 27 , wherein the medium comprises serum. 
     
     
         53 . The cell culture of  claim 27 , wherein the stem cells are mammalian stem cells. 
     
     
         54 . The cell culture of  claim 27 , wherein the progenitor cells are mammalian progenitor cells. 
     
     
         55 . The cell culture of  claim 27 , wherein the progenitor cells are neuronal progenitor cells, endothelial progenitor cells, erythroid progenitor cells, cardiac progenitor cells, oligodendrocyte progenitor cells, retinal progenitor cells, or hematopoietic progenitor cells. 
     
     
         56 . The cell culture of  claim 27 , wherein the cell culture further comprises feeder cells. 
     
     
         57 . The cell culture of  claim 27 , wherein levels of α-ketoglutarate relative to succinate in the medium maintains pluripotency of the cells. 
     
     
         58 . The cell culture of  claim 57 , wherein the α-ketoglutarate relative to succinate level is at least 0.05, 0.10, 0.15, or 0.20.