Transdifferentiation of epidermal basal cells into neural progenitor cells, neuronal cells and/or glial cells

Abstract

Disclosed is a method of transdifferentiating an epidermal basal cell into a cell having one or more morphological, physiological and/or immunological features of a neural progenitor, neuronal, or glial cell by culturing a proliferating epidermal basal cell population derived from the skin of a mammalian subject; exposing the epidermal basal cell(s) to an antagonist of bone morphogenetic protein (BMP), such as fetuin, noggin, chordin, gremlin, or follistatin; and growing the cell(s) in the presence of at least one antisense oligonucleotide comprising a segment of a human MSX1 gene and/or a segment of a human HES1 gene, or homologous non-human counterpart of either of these. Also disclosed is a transdifferentiated cell of epidermal origin and cell cultures derived therefrom. In addition, methods of using the inventive transdifferentiated cell(s) and cell cultures to identify a novel nerve growth factor or to screen a potential chemotherapeutic agent by detecting the presence or absence of an effect, in vitro, on a morphological, physiological and/or molecular biological property of the transdifferentiated cell(s) are described, as is a method of using the transdifferentiated cell(s) and cell cultures to screen a potential chemotherapeutic agent to treat a nervous system disorder of genetic origin. A kit useful for practicing the methods is disclosed