Conversion of non-neuronal cells into neurons: transdifferentiation of epidermal cells

A transdifferentiated cell having a morphological, physiolooical and/or immunological feature of a viable neuronal cell, comprising:

• an epidermal basal cell transfected with one or more expression vectors comprising a CMV promoter sequence operatively linked to a DNA(s) encoding the neurogenic transcription factor NeuroD1, NeuroD2, ASH1, Zic1, Zic3, or MyT1, wherein the DNA encoding the neurogenic transcription factor is of human origin, or is a non-human homologous counterpart or a gene encoding any of these, wherein said cell is treated with at least one antisense oligonucleotide comprising a segment(s) of human MSX1 gene or human HES1 gene, or non-human homologous counterpart thereof, and wherein said cell was grown in the presence of a retinoid and at least one neurotrophin, thereby transdifferentiating said epidermal cell into a cell comprising one or more morphological neurite-like process(es) at least about 50 micrometers in length and expressing at least one neural-specific antigen selected from the group consisting of neurofilament M, neural-specific tubulin, neural-specific enolase, and microtubule associated protein 2.

A kit for converting epidermal basal cells to cells that comprise one or more morphological neurite-like processes at least about 50 micrometers in length and express at least one neural-specific antigen selected from the group consisting of neurofilament M, neural-specific tubulin, neural-specific enolase, and microtubule associated protein 2, said kit comprising:

• one or more eukaryotic expression vector(s) containing cDNA encoding a neurogenic transcription factor, or fragment thereof, from the group consisting of NeuroD1, NeuroD2, ASH1, Zic1, Zic3, and MyT1, or a non-human homologous counterpart of any of these;
• at least one antisense oligonucleotide corresponding to the human MSX1 gene, the human HES1 gene, or a non-human homologous counterpart of either of these;
• a retinoid and at least one neurotrophin from the group consisting of BDNF, NGF, NT-3, and NT-4.

The kit of claim 5, further comprising instruction for use with a patient's claims 24-26 are canceled.

A transdifferentiated epiderinal basal cell having a morphological, physiological and/or immunological feature of a viable neuronal cell comprising:

• a cell of epidermal basal cell origin which displays one or more morphological neurite-like process(es) at least about 50 micrometers in length and expresses at least one neural-specific antigen selected from the group consisting of neurofilament M, neural-specific tubulin, neural-specific enolase, and microtubule associated protein 2.

A transdifferentiated cell comprising a cell of basal epidermal origin which displays a morphological, physiological and/or immunological feature of an astroglial cell and wherein said immunological feature is expression of glial fibrillary acidic protein (GFAP).