Methods for reprogramming cells and uses thereof

1. A population of in vitro human neural multipotent or unipotent cells derived from the reprogramming of a somatic cell, progenitor cell or stem cell, wherein the in vitro human neural multipotent or unipotent cells possess all of the following characteristics:

exhibit a non-forced gene expression profile comprising:

(a) reduced expression level of one or more markers specific to the somatic cell, progenitor cell, or stem cell from which the neural multipotent or unipotent cell is derived;

(b) maintained expression of one or more markers specific to the somatic cell, progenitor cell, or stem cell from which the neural multipotent or unipotent cell is derived; and

(c) expression of markers and characteristics of a neural multipotent or unipotent cell;

are not differentiated from a pluripotent cell;

are not cancerous cells;

give rise to a higher number of neuronal and/or glial cells compared to a neuroprogenitor cell isolated from a human and cultured under identical culture conditions as said population of neural multipotent or unipotent cells; and

do not exhibit uncontrolled growth, teratoma formation, and tumor formation in vivo;

wherein the population comprises cells comprising at least one polypeptide selected from the group consisting of:

Musashi1 (Msi1);

Neurogenin2 (Ngn2);

Achaete-Scute Homolog 1 (Ascl1);

SRY (sex determining region Y)-box 2 (Sox2);

Zic Family Member 1 (ZIC1); and

methyl-CpG binding domain protein 2 (MBD2).

2. The population of claim 1 , wherein the population comprises neural stem cells, neural precursor cells, neural progenitor cells, or neuroblasts.

3. The population of claim 1 , wherein the population comprises cells that can differentiate into a plurality of neural progenitor, precursor, or somatic cells.

4. The population of claim 1 , wherein the population comprises cells having the ability to proliferate for more than 30 population doublings.

5. The population of claim 1 , wherein the population comprises cells capable of maintaining telomerase activity through to at least about 30 population doublings.

6. The population of claim 1 , wherein the doubling time of the cell population is less than 7 days.

7. The population of claim 6 , wherein the doubling time of the cell population is less than 3 days.

8. An in vitro population of human neural multipotent or unipotent cells derived from the reprogramming of a somatic cell, progenitor cell or stem cell, wherein the population possesses all of the following characteristics:

i) expression of one or more markers selected from the group consisting of Sox2, Nestin, Glial Fibrillary acidic protein (GFAP), β III-tubulin, CNPase, MAP2, Msi1, and Ngn2;

ii) is capable of being cultured in suspension or as an adherent culture;

iii) is capable of proliferating or growing without the presence of an exogenous reprogramming agent for over 1 month; and

iv) exhibits a stable, non-forced gene expression profile comprising:

(a) reduced expression level of one or more markers specific to a somatic cell, progenitor cell or stem cell from which the neural multipotent or unipotent cell is derived;

(b) expression of markers and characteristics of a neural multipotent or unipotent cell;

v) comprises cells comprising at least one polypeptide selected from the group consisting of:

Musashi1 (Msi1);

Neurogenin2 (Ngn2);

Achaete-Scute Homolog 1 (Ascl1);

SRY (sex determining region Y)-box 2 (Sox2);

Zic Family Member 1 (ZIC1); and

methyl-CpG binding domain protein 2 (MBD2);

vi) gives rise to a higher number of neuronal and/or glial cells compared to a neuroprogenitor cell isolated from a human and cultured under identical culture conditions as said population of neural multipotent or unipotent cells;

and wherein the neural multipotent or unipotent cells possess one or more of the following characteristics:

vii) form neurospheres in the neurosphere-colony formation assay;

viii) capable of dividing every 36 hours at low passage;

ix) capable of differentiation into one or more of a neuronal cell, an astrocyte, or an oligodendrocyte;

x) one or more morphological processes characteristic of immature axons and/or dendrites and greater than one cell diameter in length;

xi) expression of at least one marker for a neurotransmitter selected from the group consisting of dopamine, acetylcholine, and gamma aminobutyric acid (GABA);

xii) capable of releasing one or more neurotrophic factors;

xiii) negative in a tumor colony forming assay;

xiv) negative for tumor growth in Severely Compromised Immuno-Deficient (SCID) mice;

xv) negative for teratoma growth in SCID mice;

xvi) capable of significantly improving one or more functional measures after placement of an adequate number of the cells into the void in a brain ablation model;

xvii) capable of significantly improving or maintaining one or more functional measures after injecting an adequate number of the cells into an Experimental Allergic Encephalomyelitis (EAE) mouse model;

xviii) capable of improving one or more functional measures more significantly than hNPCs in CNS injury or neurodegenerative models;

xix) capable of maintaining telomerase activity through to at least about 30 population doublings;

xx) able to proliferate for more than 30 population doublings; and

xxi) has an average cell population doubling time of less than 7 days.

9. The population of claim 8 , wherein the population comprises neural stem cells, neural precursor cells, neural progenitor cells or neuroblasts.

10. The population of claim 8 , wherein the population comprises cells that can differentiate into a plurality of neural progenitor, precursor, or somatic cells.

11. A plurality of cells isolated from the population of claim 1 , wherein the cells are organized within a three dimensional structure.

12. A plurality of cells isolated from the population of claim 8 , wherein the cells are organized within a three dimensional structure.

13. A pharmaceutically-acceptable composition comprising cells according to the population of claim 1 for transplantation into a subject.

14. A pharmaceutically-acceptable composition comprising cells according to the population of claim 8 for transplantation into a subject.

15. A pharmaceutically-acceptable composition comprising cells according to claim 11 for transplantation into a subject.

16. A pharmaceutically-acceptable composition comprising cells according to claim 12 for transplantation into a subject.

17. The population of claim 1 , wherein the population expresses Glial fibrillary acidic protein (GFAP) and Microtubule-associated protein 2 (MAP2).

18. The population of claim 8 , wherein the population expresses Glial fibrillary acidic protein (GFAP) and Microtubule-associated protein 2 (MAP2).

19. The population of claim 1 , wherein the population expresses synaptotagmin 1.

20. The population of claim 8 , wherein the population expresses synaptotagmin 1.