Cell cycle regulation and differentiation

• US 20090258423A1
• Filed: 01/26/2009
• Published: 10/15/2009
• Est. Priority Date: 07/26/2006
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: DUGAS, Jason, Barres, Ben A.
• Granted Patent: US 7,897,359 B2
• Time in Patent Office: Days
• US Class Current: 435/377
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2501/405 Cell cycle regulated proteins, e.g. cyclins, cyclin-dependant kinases
• CPC Class Codes: C12N 2501/60 Transcription factors
• CPC Class Codes: C12N 5/0622 Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
• CPC Class Codes: G01N 2333/4706 stimulating, promoting or activating activity
• CPC Class Codes: G01N 33/5058 Neurological cells

Abstract

The present invention provides compositions and methods for regulating neural cell proliferation or differentiation. The present invention also provides methods for selecting for bioactive agents effective in regulating proliferation or differentiation.

Claims

1. A method of regulating proliferation or differentiation of a neural cell comprising contacting said neural cell with a bioactive agent effective in modulating the activity or expression level of transcription factor ZFP536 or KLF9, thereby regulating said proliferation or differentiation of said neural cell.

13. The method of claim 1, wherein said neural cell is a glial cell.

14. The method of claim 13, wherein said glial cell has undergone no more than four divisions.

15. The method of claim 13, wherein said glial cell is an immature OL or an oligodendrocyte precursor cell (OPC).

16. The method of claim 1, wherein said regulation reduces proliferation or promotes differentiation of said neural cell.

17. The method of claim 1, wherein said regulation promotes proliferation or reduces differentiation of said neural cell.

2. A method of regulating proliferation or differentiation of a neural cell comprising contacting said neural cell with a bioactive agent effective in modulating the activity or expression level of p57^Kip2 in said neural cell, thereby regulating said proliferation or differentiation of said neural cell.

25. The method of claim 2, wherein said neural cell is a glial cell.

26. The method of claim 25, wherein said glial cell has undergone no more than four divisions.

27. The method of claim 25, wherein said glial cell is an immature OL or an oligodendrocyte precursor cell (OPC).

28. The method of claim 2 wherein said regulation reduces proliferation or promotes differentiation of said neural cell.

29. The method of claim 2 wherein said regulation promotes proliferation or reduces differentiation of said neural cell.

3. A method of regulating proliferation or differentiation of a neural cell comprising contacting said neural cell with a bioactive agent effective in modulating the activity or expression level of one or more oligodendrocyte-regulated transcription factors or myelin-enriched genes implicated in a discrete phase of differentiation of said neural cell.

5. The method of claim 3, wherein said discrete phase of differentiation is an early phase of oligodendrocyte (OL) differentiation characterized by differential expression of one or more genes depicted in FIG. 12, 16, or 19.

6. The method of claim 3, wherein the discrete phase of differentiation is a late phase of OL differentiation characterized by differential expression of one or more genes depicted in FIG. 13, 17, or 20.

30. The method of claim 3, wherein said neural cell is a glial cell.

31. The method of claim 30, wherein said glial cell has undergone no more than four divisions.

32. The method of claim 30, wherein said glial cell is an immature OL or an oligodendrocyte precursor cell (OPC).

33. The method of claim 3 wherein said regulation reduces proliferation or promotes differentiation of said neural cell.

34. The method of claim 3 wherein said regulation promotes proliferation or reduces differentiation of said neural cell.

4. (canceled)

7-12. -12. (canceled)

18-24. -24. (canceled)