Nuclear Reprogramming Factor

• US 20090068742A1
• Filed: 12/06/2006
• Published: 03/12/2009
• Est. Priority Date: 12/13/2005
• Status: Active Grant

• Current Assignee: Kyoto University
• Original Assignee: Kyoto University
• Inventors: Yamanaka, Shinya
• Granted Patent: US 8,048,999 B2
• Time in Patent Office: Days
• US Class Current: 435/455
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C12N 2501/60 Transcription factors
• CPC Class Codes: C12N 2501/602 Sox-2
• CPC Class Codes: C12N 2501/603 Oct-3/4
• CPC Class Codes: C12N 2501/604 Klf-4
• CPC Class Codes: C12N 2501/605 Nanog
• CPC Class Codes: C12N 2501/606 c-Myc
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus
• CPC Class Codes: C12N 5/0696 Artificially induced pluripotent stem cells, e.g. iPS

Abstract

There is provided a nuclear reprogramming factor for a somatic cell, which comprises a gene product of each of the following three kinds of genes: an Oct family gene, a Klf family gene, and a Myc family gene, as a means for inducing reprogramming of a differentiated cell to conveniently and highly reproducibly establish an induced pluripotent stem cell having pluripotency and growth ability similar to those of ES cells without using embryo or ES cell.

Claims

1. A nuclear reprogramming factor for a somatic cell, which comprises a gene product of each of the following three kinds of genes:

an Oct family gene, a Klf family gene, and a Myc family gene.

2. The factor according to claim 1, which comprises a gene product of each of the following three kinds of genes:

Oct3/4, Klf4, and c-Myc.

3. The factor according to claim 1, which further comprises a gene product of the following gene:

a Sox family gene.

4. The factor according to claim 3, which comprises a gene product of Sox2.

5. The factor according to claim 1, which comprises a cytokine together with a gene product of the Myc family gene.

6. The factor according to claim 5, wherein the cytokine is basic fibroblast growth factor (bFGF) and/or stem cell factor (SCF).

7. The factor according to claim 1, which further comprises a gene product of the following gene:

TERT gene.

8. The factor according to claim 1, which further comprises a gene product or gene products of one or more kinds of the following genes:

SV40 Large T antigen, HPV16 E6, HPV16 E7, and Bmil.

9. The factor according to claim 1, which further comprises a gene product or gene products of one or more kinds of the following genes:

Fbx15, Nanog, ERas, ECAT15-2, Tcl1, and β

-catenin.

10. The factor according to claim 1, which further comprises a gene product or gene products of one or more kinds of the following genes:

ECAT1, Esg1, Dnmt3L, ECAT8, Gdf3, Sox15, ECAT15-1, Fthl17, Sall4, Rex1, UTF1, Stella, Stat3, and Grb2.

11. A method for preparing an induced pluripotent stem cell by nuclear reprogramming of a somatic cell, which comprises contacting the nuclear reprogramming factor according to claim 1 with the somatic cell in the absence of eggs, embryos, or embryonic stem (ES) cells.

12. The method according to claim 11, wherein the somatic cell is a human cell.

13. An induced pluripotent stem cell obtained by the method according to claim 11.

14. A somatic cell derived by inducing differentiation of the induced pluripotent stem cell according to claim 13.

15. A method for improving differentiation ability and/or growth ability of a cell, which comprises contacting the nuclear reprogramming factor according to claim 1 with the cell.

16. The method according to claim 15, wherein the cell is a human cell.

17. A cell obtained by the method according to claim 15.

18. A somatic cell derived by inducing differentiation of the cell according to claim 17.

21. The cell according to claim 13, which is a human cell.

22. The cell according to claim 13, which is a mouse cell.

23. The cell according to claim 14, which is a human cell.

24. The cell according to claim 14, which is a mouse cell.

25. The method according to claim 11, wherein the nuclear reprogramming factor comprises a gene product of each of the following three kinds of genes:

an Oct family gene, a Klf family gene, and a Myc family gene.

26. The method according to claim 11, wherein the nuclear reprogramming factor comprises a gene product of each of the following three kinds of genes:

Oct3/4, Klf4, and c-Myc.

27. The method according to claim 25, wherein the nuclear reprogramming factor further comprises a gene product of the following gene:

a Sox family gene.

28. The method according to claim 27, wherein the nuclear reprogramming factor comprises a gene product of Sox2.

29. The method according to claim 11, wherein the contacting is in the absence of eggs, embryos, or embryonic stem (ES) cells.

19. A nuclear reprogramming factor for a somatic cell, which comprises a gene product of each of the following three kinds of genes:

an Oct family gene, a Klf family gene, and a cytokine.

20. The factor according to claim 19, wherein the cytokine is bFGF and/or SCF.