Stem Cell Renewal And Differentiation in Spermatogenesis

描述(申请人提供)：许多组织和器官中的细胞在我们的一生中不断补充。这是由干细胞完成的，干细胞可以平衡自我更新和更多分化的细胞类型。控制这种平衡的机制尚不清楚。在干细胞维持的组织中，分化的子代在产生特定组织类型的细胞之前经历有丝分裂扩张。控制转运体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，在这种情况下，干细胞子代在自我更新和分化之间进行选择，而过渡扩增性腺细胞则切换到精母细胞的发育。生殖细胞分裂四次；调节这种分裂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协作，协调精母细胞的转变。我们发现，体细胞信号促进干细胞子体的分化，而其他实验室则发现了促进自我更新的信号。Aim 2测试了自我更新和差异化确实被这些相互竞争的信号所平衡的假设，然后研究它们是如何竞争的。为了产生并开始测试其他候选因子和信号通路的生物学假说，我们对自我更新细胞或它们的分化子细胞进行了转录图谱分析。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.