果蝇生殖干细胞自我更新的调控网络。
A regulatory network of Drosophila germline stem cell self-renewal.
机构信息
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Drosophila RNAi Screening Center, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Dev Cell. 2014 Feb 24;28(4):459-73. doi: 10.1016/j.devcel.2014.01.020.
Stem cells possess the capacity to generate two cells of distinct fate upon division: one cell retaining stem cell identity and the other cell destined to differentiate. These cell fates are established by cell-type-specific genetic networks. To comprehensively identify components of these networks, we performed a large-scale RNAi screen in Drosophila female germline stem cells (GSCs) covering ∼25% of the genome. The screen identified 366 genes that affect GSC maintenance, differentiation, or other processes involved in oogenesis. Comparison of GSC regulators with neural stem cell self-renewal factors identifies common and cell-type-specific self-renewal genes. Importantly, we identify the histone methyltransferase Set1 as a GSC-specific self-renewal factor. Loss of Set1 in neural stem cells does not affect cell fate decisions, suggesting a differential requirement of H3K4me3 in different stem cell lineages. Altogether, our study provides a resource that will help to further dissect the networks underlying stem cell self-renewal.
干细胞在分裂时具有产生两种不同命运细胞的能力
一个细胞保留干细胞特性，另一个细胞注定要分化。这些细胞命运是由细胞类型特异性的遗传网络决定的。为了全面鉴定这些网络的组成部分，我们在果蝇雌性生殖干细胞（GSCs）中进行了一项大规模的 RNAi 筛选，涵盖了大约 25%的基因组。该筛选鉴定了 366 个影响 GSC 维持、分化或卵发生过程中其他过程的基因。将 GSC 调节因子与神经干细胞自我更新因子进行比较，确定了共同和细胞类型特异性的自我更新基因。重要的是，我们鉴定出组蛋白甲基转移酶 Set1 是 GSC 特异性的自我更新因子。在神经干细胞中缺失 Set1 不会影响细胞命运决定，这表明 H3K4me3 在不同的干细胞谱系中具有不同的需求。总之，我们的研究提供了一个资源，将有助于进一步剖析干细胞自我更新的网络。
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