Glial restricted precursors during CNS development

描述（由申请人提供）：我们分离并鉴定了一种胶质限制性前体细胞（GRP细胞），该细胞在胚胎年龄13.5（E13.5）时存在于大鼠脊髓中，并可在体外和体内产生少突胶质细胞和星形胶质细胞。我们已经证明，GRP细胞是从E10.5脊髓的多能神经上皮干细胞（NEP细胞）直接产生的后代。在稍后的时间点，产生少突胶质细胞的神经胶质前体群体，O-2A/OPC，在脊髓的腹侧一半中形成。不局限于脊髓腹侧的GRP细胞在体外可产生O-2A/OPC细胞。我们现在测试的假设，从GRP细胞的O-2A/OPCs的产生是依赖于脊髓腹侧的一半存在的因素，可以抑制背侧衍生的信号。此外，我们建议确定脊髓背侧区域的GRP细胞的作用，特别是它们作为星形胶质细胞祖先的潜在作用。 在脊髓中，NEP细胞、GRP细胞和O-2A/OPCs之间似乎存在直接的直系关系，包括顺序谱系限制。我们现在将检验胚胎大脑中也发生类似过程的假设。除了在体外表征推定的脑源性GRP细胞外，我们还将通过将细胞移植到新生儿CNS中来确定我们在组织培养中可以识别的特性是否在体内保留。 最后，我们将测试的假设，谱系限制和细胞类型，在胚胎胶质细胞生成过程中所涉及的是保守的新生儿和成人中枢神经系统胶质细胞生成。我们建议从成体脊髓源性干细胞和原代成体组织中产生GRP细胞。

DESCRIPTION (provided by applicant): We have isolated and characterized a glial restricted precursor cell (GRP cell) that is present at embryonic age 13.5 (E13.5) in the rat spinal cord and can give rise to oligodendrocytes and astrocytes in vitro and in vivo. We have shown that GRP cells are generated as a direct progeny from the multipotent neuroepithelial stem cells (NEP cells) of the E10.5 spinal cord. At a later time point, the glial precursor population that gives rise to oligodendrocytes, the O-2A/OPC, is formed in the ventral half of the spinal cord. GRP cells, which are not restricted to the ventral half of the spinal cord, can give rise to O-2A/OPC cells in vitro. We now test the hypothesis that the generation of O-2A/OPCs from GRP cells is dependent on factors present in the ventral half of the spinal cord and can be inhibited by dorsally derived signals. In addition, we propose to determine the role of GRP cells in the dorsal region of the spinal cord, and in particular their potential role as an ancestor of astrocytes. In the spinal cord, there appears to be a direct lineal relationship, involving sequential lineage restrictions, between NEP cells, GRP cells and O-2A/OPCs. We will now test the hypothesis that a similar process occurs in the embryonic brain. In addition to the characterization of putative brain derived GRP cells in vitro, we will determine whether the properties we can identify in tissue culture are retained in vivo by transplanting the cells into the neonatal CNS. Finally we will test the hypothesis that the lineage restrictions and cell types that are involved during gliogenesis in the embryo are conserved during gliogenesis in the neonatal and adult CNS. We propose to generate GRP cells from adult spinal cord- derived stem cells and from primary adult tissue.