FATE OF SPERMATOGONIAL STEM CELLS

描述（改编自研究者摘要）：精子发生是 一种复杂的细胞过程，由有丝分裂开始， 精原干细胞。 本申请的长期目标是 为了更好地理解这些初始步骤的规则， 精子发生，即精原细胞更新、分化或死亡。 申请人已成功分离出高纯度的 大鼠A型精原细胞，并证明这些细胞表达c-kit 受体的 干细胞因子（SCF）也磷酸化这种受体的类型 一个精原细胞 利用这一发现作为基准，申请人现在 描述了进一步研究精原细胞的三个具体目的， 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bFGF对精原细胞存活、更新和 体外分化。 可溶性和膜结合形式的SCF 将被研究。 具体目标B将研究作用机制 SCF在精原细胞中的表达。 在这里，主要目标是 表征A型细胞中的信号转导途径， 由SCF激活。 此外，路径将与 精原细胞存活、更新和/或分化。 最后，具体 目的验证端粒酶仅存在于精原细胞的假说 而这种关键酶的缺失与转化为 减数分裂 申请人强调， 分离的精原细胞，因为它可能与未来的移植研究有关 干细胞来重建受损或受损的睾丸。

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.