Stem Cell Renewal And Differentiation in Spermatogenesis

描述（由申请人提供）：许多组织和器官内的细胞在我们的一生中不断补充。这是由干细胞完成的，干细胞平衡了自我更新和更分化的细胞类型。控制这种平衡的机制尚不清楚。在由干细胞维持的组织中，分化中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。控制转运放大的机制也不清楚。这两种现象在果蝇精子发生中都有表现，其中干细胞子体在自我更新和分化之间进行选择，并且过境扩增生殖细胞切换到精母细胞发育。生殖腺细胞分裂四次;计数和效应器机制调节这是未知的。目的1：验证生殖细胞在精母细胞转化过程中，与周围的体细胞相互协调的假设。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促进自我更新的信号。目的2检验自我更新和分化确实被这些竞争信号平衡的假设，然后研究它们如何竞争。为了产生和开始测试其他候选因子和信号通路的生物学假设，这些因子和信号通路在更新和分化之间起着立法作用，我们对自我更新细胞或其分化的子细胞进行了转录谱分析。目标3提议完成这些研究，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.