FATE OF SPERMATOGONIAL STEM CELLS

描述(改编自《调查者摘要》)：精子发生 一种复杂的细胞过程，由有丝分裂类型启动 精原干细胞。此应用程序的长期目标是 为了更好地理解这些初始步骤的调节 精子发生，即精原细胞更新、分化或死亡。 申请人已成功地分离出高度纯净的 大鼠A型精原细胞表达c-kit 受体。干细胞因子(SCF)也使该受体磷酸化。 精原细胞。以这一发现为底板，申请人现在 描述了进一步研究精原细胞的三个具体目标 生命周期。 具体目标A将检查SCF单独和与 白血病抑制因子和碱性成纤维细胞生长因子对精原细胞存活、更新和发育的影响 体外分化。可溶性和膜结合型SCF 将会被研究。特定目标B将研究其作用机制 精原细胞群体中干细胞的数量。在这里，主要目标是 研究A型细胞中信号转导通路(S)的特征 由SCF激活。此外，这条路径(S)将与 精原细胞的存活、更新和/或分化。最后，具体 目的C将检验端粒酶仅限于精原细胞的假设 而这种关键酶的丧失与转化为 减数分裂。申请人强调在以下方面工作的潜在意义 分离的精原细胞，可能与未来的移植研究有关 干细胞以重新填充受损或无法手术的睾丸。

DESCRIPTION (Adapted from the Investigator's Abstract): Spermatogenesis is a complex cellular process that is initiated with mitotic divisions of type A spermatogonial stem cells. The long-term objective of this application is to understand better the regulation of these initial steps of spermatogenesis, namely spermatogonial renewal, differentiation, or death. The applicant has succeeded in the isolation of highly pure populations of rat type A spermatogonia and demonstrated that these cell express the c-kit receptor. Stem cell factor (SCF) also phosphorylates this receptor in type A spermatogonia. Using this finding as a baseboard, the applicant now describes three Specific Aims to further the study of the spermatogonial life cycle. Specific Aim A will examine the effect of SCF, alone and in combination with leukemia inhibiting factor and bFGF, on spermatogonial survival, renewal and differentiation in vitro. Both the soluble and membrane bound forms of SCF will be studied. Specific Aim B will investigate the mechanisms of action of SCF in the spermatogonial population. Here, the principal objective is to characterize the signal transduction pathway(s) in type A cells which is activated by SCF. Also, the pathway(s) will be associated with spermatogonial survival, renewal and/or differentiation. Finally, Specific Aim C will test the hypothesis that telomerase is limited to spermatogonia and that the loss of this key enzyme is associated with the transition into meiosis. The applicant stresses the potential significance of work on isolated spermatogonia as it may relate to future studies for the transplant of stem cells to repopulate damaged or inoperative testes.