CDOn: A Novel Marker of Neuronal Stem Cells

描述(申请人提供)：干细胞活性已在各种成人组织和器官中被报道，包括成人大脑中的一些离散区域。哺乳动物中枢神经系统中具有自我更新和分化为所有神经细胞类型的细胞池的鉴定引起了神经生物界的极大兴奋，因为它与脑再生、损伤和肿瘤有关。我们能否利用干细胞的再生能力来减轻神经系统疾病和损伤的负担，取决于对这些细胞的基本生物学的了解。成体干细胞研究的进展取决于清楚地识别和分离离散的细胞群，确定这些细胞的特征，以及破译周围环境中指示这些细胞是保持干细胞身份还是分化的信号。我们之前分离到了一个细胞表面受体CDON，它的表达模式与成人中枢神经系统中与干细胞活动相关的区域惊人地一致。有趣的是，这一基因功能的丧失会导致微型性全前脑畸形。本文提出的实验目的是探索CDON受体的表达是否可能描绘出成人大脑中缓慢循环的干细胞的超群。我们计划建立干细胞生态位中表达CDON的细胞的身份，并证实CDON表达作为体外和体内特异性分离这些细胞的标记的潜在有用性。因为CDON是一种受体，我们相信揭示干细胞利基中表达CDON受体的细胞与不表达CDON受体的细胞的身份将有助于深入了解干细胞利基微环境中的细胞如何对外部提示做出不同的反应。

DESCRIPTION (provided by applicant): Stem cell activity has been reported in various adult tissues and organs, including some discrete regions within the adult brain. The identification of a pool of cells within the mammalian CNS with the properties both to self-renew as well as differentiate into all neural cell types has generated much excitement in the neurobiology community because of its relevance to brain regeneration, injury and neoplasia. Our ability to harness the regenerative capacity of stem cells to reduce the burden of neurological disease and damage hinges on understanding the fundamental biology of these cells. Making progress in adult stem cell research is dependent on clearly identifying and isolating discrete cell populations, characterizing these cells, as well as on deciphering signals in the surrounding environment that instruct these cells whether to remain as stem cells or to differentiate. We previously isolated a cell surface receptor, CDOn, whose expression pattern strikingly coincides with regions in the adult central nervous system associated with stem cell activity. Interestingly, the loss of this gene function results in a microform of holoprosencephaly. The purpose of the experiments proposed here are to explore the possibility that CDOn receptor expression delineates the sup-population of slowly cycling stem cells in the adult brain. We plan to establish the identity of the cells in the stem cell niche that express CDOn and to substantiate the potential usefulness of CDOn expression as a marker for specifically isolating these cells in vitro and in vivo. Because CDOn is a receptor, we believe that revealing the identity of cells in the stem cell niche that express the CDOn receptor in comparison to cells that do not will yield insights into how cells respond differently to extrinsic cues within the microenvironment of the stem cell niche.