发掘启动减数分裂的基因网络

减数分裂是有性生殖过程中产生单倍体配子的核心环节。虽然有丝分裂向减数分裂转化的一些外源信号已被发现，内源因子和机制待解，因而操纵生殖细胞正确起始减数分裂是实现体外配子形成的一大障碍。我们以果蝇为模式发掘启动减数分裂的基因网络。我们用激光显微切割准确分离了野生型有丝分裂和减数分裂的生殖细胞；利用一系列导致生殖细胞发育停滞的突变获得了富集有丝分裂或减数分裂的生殖细胞，然后进行了大规模转录组RNA-seq。从转录后的差异性表达、可变剪切、3’UTR变化等方面初步分析了有丝和减数分裂的广泛差异。我们将更精细地分离减数分裂前期的生殖细胞，并深入分析比较野生型和突变体中有丝分裂和减数分裂细胞的表达谱特征。同时，利用高通量数据找到候选基因进行遗传筛选，并对筛选得到的重要因子进行体内外功能研究。如果关键因子具有高度保守性，我们还将构建哺乳动物模型解析减数分裂的启动机制。

Meiosis, which reduces a diploid germ cell to a haploid gamete, is the fundamental event for sexual reproduction. Although a few external cues that trigger meiosis have been identified, the internal program that switches germ cells from mitotic to meiotic track is largely unknown. Meiosis remains the major obstacle for in vitro reconstitution of gametogenesis. We sought to explore the genetic program that governs the initiation of meiosis in Drosophila. Taking advantage of the accurate selection by laser microdissection from wildtype testes and the mutants that arrest the germ cells at mitotic or meiotic stage, we obtained massive transcriptome RNA-seq data and carried out preliminary high throughput analyses (differential expression, alternative splicing, and 3’UTR profiling) to look for the differences between mitotic and meiotic cells. These provided us candidate genes for further genetic screen and functional analyses. Moreover, we will extend our study to the mammalian system once we discover the highly conserved key factors in meiosis initiation.