Method for producing pluripotent stem cells

A method for enhancing efficiency of differentiation of induced pluripotent stem cells (iPSCs) towards neuronal lineages, in vitro, said method comprising:

• introducing into induced human pluripotent stem cells, at least one molecule selected from the group consisting of
• (a) a nucleic acid that encodes a mutant human TET1 protein having the amino acid sequence selected from the group consisting of SEQ ID NO:
• 2, 4 and 6, and partial sequences thereof having at least amino acids 1 through 613 of SEQ ID NO:
• 2, 4 and 6, said amino acid sequence incorporating the binding domain at amino acids 585 to 613 and said mutant human TET1 protein having the amino acid sequence of SEQ ID NO:
• 46 inserted between the first and second amino acid from the N-terminus, wherein said insertion results in the substitution of the serine at the second position with another amino acid and
• (b) a vector into which a nucleic acid that encodes the mutant human TET1 protein has been inserted, to provide transformed (iPSCs) that express said mutant human TET1 protein,
• wherein said expressed mutant human TET1 protein has enhanced stability as compared to the corresponding non-mutant human TET1 protein selected from the group consisting of SEQ ID NO:
• 2, 4 and 6, wherein said enhanced stability is determined by Western blotting and wherein expressed mutant human TET1 protein enhances the efficiency of differentiation of said induced pluripotent stem cells.

A method for enhancing efficiency of differentiation of human induced pluripotent stem cells (iPSCs) towards neuronal lineages, in vitro, said method comprising:

• introducing together into human somatic cells reprogramming factors for induction to induced pluripotent stem cells, and at least one molecule selected from the group consisting of
• (a) a nucleic acid that encodes a mutant human TET1 protein having the amino acid sequence selected from the group consisting of SEQ ID NO:
• 2, 4 and 6, and partial sequences thereof having at least amino acids 1 through 613 of SEQ ID NO:
• 2, 4 and 6, said amino acid sequence incorporating the binding domain at amino acids 585 to 613 and said mutant human TET1 protein having the second amino acid from the N-terminus substituted with another amino acid and
• (b) a vector into which a nucleic acid that encodes said mutant human TET1 protein has been inserted, to provide iPSCs from somatic cells that express said mutant human TET1 protein;
• wherein said expressed mutant human TET1 protein has enhanced stability as compared to the corresponding non-mutant human TET1 protein selected from the group consisting of SEQ ID NO:
• 2, 4 and 6, wherein said enhanced stability is determined by Western blotting and wherein expressed mutant human TET1 protein enhances the efficiency of differentiation of said induced pluripotent stem cells.

A method for enhancing efficiency of differentiation of induced pluripotent stem cells (iPSCs) towards neuronal lineages, in vitro, said method comprising:

• introducing together into human somatic cells reprogramming factors for induction to induced pluripotent stem cells, and at least one molecule selected from the group consisting of
• (a) a nucleic acid that encodes a mutant human TET1 protein having the amino acid sequence selected from the group consisting of SEQ ID NO:
• 2, 4 and 6, and partial sequences thereof having at least amino acids 1 through 613 of SEQ ID NO:
• 2, 4 and 6, said amino acid sequence incorporating the binding domain at amino acids 585 to 613 and said mutant human TET1 protein having the amino acid sequence of SEQ ID NO:
• 46 inserted between the first and second amino acid from the N-terminus, wherein said insertion results in the substitution of the serine at the second position with another amino acid and
• (b) a vector into which a nucleic acid that encodes the mutant human TET1 protein has been inserted, to provide iPSCs from somatic cells that express said mutant human TET1 protein,
• wherein said expressed mutant human TET1 protein has enhanced stability as compared to the corresponding non-mutant human TET1 protein selected from the group consisting of SEQ ID NO:
• 2, 4 and 6, wherein said enhanced stability is determined by Western blotting and wherein expressed mutant human TET1 protein enhances the efficiency of differentiation of said induced pluripotent stem cells.