Direct conversion of cells to cells of other lineages

Abstract

Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

That which is claimed is: 
     
         1 . A method of converting human pluripotent cells into induced neuronal cells, the method comprising:
 contacting a population of human pluripotent cells with an effective dose of a neuron reprogramming (NR) system comprising an Ascl agent and an DLX2 agent as neuron reprogramming (NR) factors for a period of time sufficient to reprogram said pluripotent cells,   wherein a population of induced neuronal cells is produced.   
     
     
         2 . The method of  claim 1 , wherein the pluripotent cells are human cells. 
     
     
         3 . The method of  claim 1 , wherein the efficiency of reprogramming said pluripotent cells to become induced neuronal cells is at least about 0.1%. 
     
     
         4 . The method of  claim 1 , wherein the pluripotent cells are reprogrammed into neuronal cells with functional properties within 10 days after contacting the cells with the reprogramming factors. 
     
     
         5 . The method of  claim 1 , wherein the pluripotent cells are induced pluripotent (iPS) cells. 
     
     
         6 . The method of  claim 1 , wherein the pluripotent cells are embryonic stem cells. 
     
     
         7 . The method of  claim 1 , wherein the Ascl agent is Ascl1. 
     
     
         8 . The method of  claim 1 , wherein the reprogramming (NR) system further comprising a Myt1 agent. 
     
     
         9 . The method of  claim 1 , wherein the induced neuronal cells are inhibitory neurons. 
     
     
         10 . An in vitro cell culture system comprising an isolated population of human pluripotent cells genetically engineered to comprise a nucleic acid vector encoding Ascl polypeptide operably linked to a promoter, and a nucleic acid vector encoding DLX2 polypeptide operably linked to a promoter. 
     
     
         11 . The cell culture system of  claim 10 , wherein the pluripotent cells are induced pluripotent (iPS) cells. 
     
     
         12 . The cell culture system of  claim 10 , wherein the pluripotent cells are embryonic stem cells. 
     
     
         13 . The cell culture system of  claim 10 , wherein the isolated population of human pluripotent cells genetically is engineered to further comprise a nucleic acid vector encoding Myt1 polypeptide operably linked to a promoter.