通过 P 体和转录协调抑制促分化基因维持果蝇肠道干细胞特性。
Coordinated repression of pro-differentiation genes via P-bodies and transcription maintains Drosophila intestinal stem cell identity.
机构信息
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
出版信息
Curr Biol. 2022 Jan 24;32(2):386-397.e6. doi: 10.1016/j.cub.2021.11.032. Epub 2021 Dec 6.
The role of processing bodies (P-bodies), key sites of post-transcriptional control, in adult stem cells remains poorly understood. Here, we report that adult Drosophila intestinal stem cells, but not surrounding differentiated cells such as absorptive enterocytes (ECs), harbor P-bodies that contain Drosophila orthologs of mammalian P-body components DDX6, EDC3, EDC4, and LSM14A/B. A targeted RNAi screen in intestinal progenitor cells identified 39 previously known and 64 novel P-body regulators, including Patr-1, a gene necessary for P-body assembly. Loss of Patr-1-dependent P-bodies leads to a loss of stem cells that is associated with inappropriate expression of EC-fate gene nubbin. Transcriptomic analysis of progenitor cells identifies a cadre of such weakly transcribed pro-differentiation transcripts that are elevated after P-body loss. Altogether, this study identifies a P-body-dependent repression activity that coordinates with known transcriptional repression programs to maintain a population of in vivo stem cells in a state primed for differentiation.
处理体（P 体）是转录后控制的关键部位，但其在成体干细胞中的作用仍知之甚少。在这里，我们报告说，成年果蝇肠道干细胞，而不是周围的分化细胞，如吸收肠细胞（ECs），含有果蝇 P 体成分 DDX6、EDC3、EDC4 和 LSM14A/B 的哺乳动物同源物。在肠祖细胞中的靶向 RNAi 筛选鉴定了 39 个先前已知和 64 个新的 P 体调节剂，包括 Patr-1，这是 P 体组装所必需的基因。依赖 Patr-1 的 P 体的缺失导致干细胞的丢失，这与 EC 命运基因 nubbin 的异常表达有关。祖细胞的转录组分析鉴定了一组这样的弱转录的促分化转录本，它们在 P 体缺失后升高。总的来说，这项研究确定了一种依赖 P 体的抑制活性，它与已知的转录抑制程序协调，以维持体内干细胞处于分化预备状态的群体。
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