Method for producing pancreatic endocrine cells, and transdifferentiation agent

Abstract

A method for producing pancreatic endocrine cells, including introducing (A), (B), (C), or (D) into somatic cells: (A) mutated GLIS1 gene having ≥85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, Pdx1 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof, (B) mutated GLIS1 gene having ≥85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, and Pdx1 gene or gene product(s) thereof. (C) GLIS1 gene or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, Pdx1 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof, and (D) mutated GLIS1 gene having ≥85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof.

1 - 14 . (canceled) 
     
     
         15 . A method for producing pancreatic endocrine cells, the method comprising:
 introducing (B) or (D) below into cultured somatic cells to transdifferentiate into a population of pancreatic endocrine cells comprising insulin-producing beta-cells:   (B) a GLIS1 gene or one or more gene products thereof,
 a Neurogenin3 gene or one or more gene products thereof, and 
 a PdX1 gene or one or more gene products thereof; and 
   (D) a GLIS1 gene or one or more gene products thereof,
 a Neurogenin3 gene or one or more gene products thereof, and 
 a MafA gene or one or more gene products thereof, 
   wherein the GLIS1 gene comprises the nucleotide sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 2, and   wherein the population of pancreatic endocrine cells are produced without undergoing an induced pluripotent stem (iPS) cell stage.   
     
     
         16 . The method for producing pancreatic endocrine cells according to  claim 15 , wherein the somatic cells are fibroblasts or mesenchymal stem cells.