中文摘要
干细胞通过不对称分裂进行自我更新，同时产生分化细胞，形成新的组织，或替代损伤或丢失的组织。但其详细机制仍不清楚。为了阐明这一不对称分裂的机制，我们以果蝇的生殖干细胞为模型系统，通过遗传学方法筛选和克隆与干细胞命运相关的新基因。我们发现小分子RNA调控基因Ago-1可能参与干细胞命运的调控。遗传功能分析表明，Ago-1依赖的小分子RNA途径在干细胞命运调控起关键作用。进一步研究表明，生殖细胞特异高表达小分子RNA（mi278）等显著增加干细胞数目从而抑制干细胞的分化。本项目力图阐明Ago-1介导的小分子RNA途径在干细胞命运调控中的作用和新机制。此外我们还探讨了小分子RNA可能下游途径Smurf/Faf基因在干细胞中的工作机制。本研究直接将小分子RNA与干细胞命运的调控直接联系起来，可以更好地理解果蝇生殖干细胞调控机制，同时为哺乳动物干细胞命运调控研究提供新思路。
英文摘要
In the adult tissues, Stem cells have the unique capacity to self-renewal and differentiate into a cell lineage for maintaining the tissue homeostasis and repairing the damage tissues. However, the mechanism of this asymmetric division is still poorly understood. In order to elucidate the mechanism and identify new genes involved in stem cell function, we used germline stem cells (GSCs) in drosophila ovary as a model, and performed a genetic screen. From our screen, we isolated a gene Ago1, known as a microRNA pathway regulator that can modulate GSCs fate. Cell clonal assay showed Ago1 is intrinsically required for GSC maintenance. Our preliminary data also showed overexpression of some microRNA results increase of GSCs number. These data demonstrated that microRNA pathway play important role in regulation of GSC fate. In this proposal, we try to understand how Ago1 regulate the GSC fate in the gene circuitry that previously we set up. We also want to figure out the following mechanistic questions: 1. What are co-factors in Ago1 complexes? 2. What are the specific small RNAs functional in GSCs? 3. What are the downstream target genes of microRNA functional in GSCs? One pathway, smurf/faf pathway could genetically interact with Ago1, and possibly downstream of microRNA pathway. In our proposal, we will elucidate
结题摘要
干细胞通过不对称分裂进行自我更新，同时产生分化细胞，形成新的组织，或替代损伤或丢失的组织。但其详细机制仍不清楚。为了阐明这一不对称分裂的机制，我们以果蝇的生殖干细胞为模型系统，通过遗传学方法筛选和克隆与干细胞命运相关的新基因。我们发现小分子RNA调控基因Ago-1可能参与干细胞命运的调控。遗传功能分析表明，Ago-1依赖的小分子RNA途径在干细胞命运调控起关键作用。进一步研究表明，生殖细胞特异高表达小分子RNA（mi278）等显著增加干细胞数目从而抑制干细胞的分化。本项目力图阐明Ago-1介导的小分子RNA途径在干细胞命运调控中的作用和新机制。此外我们还探讨了小分子RNA可能下游途径Smurf/Faf基因在干细胞中的工作机制。本研究直接将小分子RNA与干细胞命运的调控直接联系起来，可以更好地理解果蝇生殖干细胞调控机制，同时为哺乳动物干细胞命运调控研究提供新思路。