Stem Cell Renewal And Differentiation in Spermatogenesis

许多组织和器官中的细胞在我们的一生中不断补充。这是 这是由干细胞完成的，干细胞可以平衡自我更新和更分化的细胞类型。的 控制这种平衡的机制尚不清楚。在由干细胞维持的组织中， 子代在产生组织特异性细胞类型之前经历有丝分裂扩增。的机制 控制过境放大也不清楚。这两种现象在果蝇中都有 精子发生，其中干细胞子代在自我更新和分化之间进行选择， 生殖细胞转换为精母细胞发育。 生殖腺细胞分裂四次;计数和效应器机制调节这是未知的。要求1 检验了生殖细胞本质上计数的假设，然后与周围的体细胞合作， 协调精母细胞的转换。 我们发现，体细胞信号促进干细胞子细胞的分化，而其他实验室 发现了一种促进自我更新的信号。目的2检验自我更新和 这些竞争信号确实平衡了差异，然后研究它们是如何竞争的。 生成并开始测试其他候选因素和信号传导的基于生物学的假设 在更新和分化之间立法的途径，我们进行了转录谱分析 自我更新的细胞或它们分化的子细胞。目标3建议完成这些研究， 对选定的候选人进行功能测试。

Cells within many tissues and organs are continually replenished throughout our lives. This is accomplished by stem cells, which balance self-renewal with more differentiated cell types. The mechanisms that control this balance are not clear. In tissues maintained by stem cells, the differentiating daughters undergo mitotic expansion before generating tissue-specific cell types. The mechanisms that control transit amplification are also not clear. Both of these phenomena are featured in Drosophila spermatogenesis, where stem cell daughters choose between self-renewal and differentiation, and where transit amplifying gonial cells switch to spermatocyte development. Gonial cells divide four times; the counting and effector mechanisms regulating this are unknown. Aim 1 tests the hypothesis that germ cells count intrinsically, and then collaborate with surrounding somatic cells to coordinate the spermatocyte transition. We discovered that a somatic cell signal promotes differentiation of stem cell daughters, while other labs discovered a signal that promotes self-renewal. Aim 2 tests the hypothesis that self-renewal and differentiation are indeed balanced by these competing signals, and then investigate how they compete. To generate and begin to test biologically-based hypotheses for other candidate factors and signaling pathways that legislate between renewal and differentiation we have conducted transcript profiling analyses of self-renewing cells or their differentiating daughters. Aim 3 proposes to complete these studies and conduct functional tests on selected candidates.