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得到补充。这是 由干细胞完成，它平衡自我更新和更多分化的细胞类型。这个 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 女儿在产生特定组织类型的细胞之前会经历有丝分裂的扩张。这些机制可以 对照过境放大情况也不清楚。这两种现象在果蝇身上都有表现 精子发生，干细胞子体在自我更新和分化之间选择的地方，以及在哪里 过渡扩增性腺细胞转变为精母细胞发育。 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。目标1 测试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，体细胞信号促进干细胞子体的分化，而其他实验室 发现了一种促进自我更新的信号。目标2检验了自我更新和自我更新 差异化确实被这些相互竞争的信号所平衡，然后调查它们是如何竞争的。 为其他候选因素和信号生成并开始测试基于生物学的假设 在更新和分化之间的立法路径我们已经进行了文字记录分析 自我更新细胞或它们的分化子细胞。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。

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.