Stem Cell Renewal And Differentiation in Spermatogenesis

描述（由申请人提供）：在我们的一生中，许多组织和器官中的细胞都在不断地补充。这是由干细胞完成的，它通过更多分化的细胞类型来平衡自我更新。控制这种平衡的机制尚不清楚。在由干细胞维持的组织中，分化的子细胞在产生组织特异性细胞类型之前经历有丝分裂扩增。控制凌日放大的机制也不清楚。这两种现象都出现在果蝇的精子发生中，干细胞子细胞在自我更新和分化之间做出选择，转运扩增的生殖细胞转向精母细胞发育。生殖细胞分裂四次；调控这一现象的计数和效应机制尚不清楚。目的1验证生殖细胞内在计数的假设，然后与周围的体细胞合作协调精母细胞的转变。我们发现体细胞信号促进了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验证了自我更新和分化确实是通过这些竞争信号来平衡的假设，然后研究它们是如何竞争的。为了产生并开始测试基于生物学的假设，以确定更新和分化之间的其他候选因子和信号通路，我们对自我更新细胞或其分化子细胞进行了转录谱分析。目标3建议完成这些研究，并对选定的候选人进行功能测试。

DESCRIPTION (provided by applicant): 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.