The recent discovery of multipotent progenitor cells in the adult central nervous system (CNS) offers the potential that these cells can be used to re-wire damaged neural circuits. These progenitor cells are propagated by relatively simple culture conditions, and implants of in vitro propagated neural stem cells can reverse and even cure neurological problems in animals. Cell-based strategies to CNS repair using both totipotent embryonic stem (ES) cells, and in vitro amplified spinal cord progenitor cells (SCPC) has restored a significant level of function to spinal cord injured rats, and overcome genetic defects in cerebellar function. In this proposal we will compare the expressed gene profiles of the totipotent ES cell, with those of the in vitro propagated neural progenitor cells isolated from the adult cerebral cortex and the spinal cord, from the cerebrospinal fluid, from fat and from the neonatal cerebellum. We will identify progenitor cell specific genes by DNA microarray analysis and characterize the developmental expression pattern of cerebellar external granule layer (EGL) progenitor cells during their differentiation into granule neurons.
The Specific Aims of the proposal will address the following questions: 1) Do the transcript profiles of in vitro amplified progenitor cells isolated from adult cerebral cortex, spinal cord, the cerebrospinal fluid, the neonatal cerebellum and fat differ from the totipotent ES cell? 2) How does the expressed gene profile change when neural progenitor cells differentiate into neurons in vitro? The proposed body of work will provide the basic information required to establish the similarity/differences between the ES cell and the adult progenitor cells at the genomic level. The results of the proposed studies will provide the basic information required to generate sufficient numbers of undifferentiated progenitor cell for therapeutic use and establish the consequences of in vitro amplification on the fate of the progenitor cell. In addition, this work will lead to studies aimed at predetermining program of an important in situ pool of neuronal precursors that can be used to repair the lost circuitry typically found in the aging CNS.
