Insulin/IGF-1 signaling and heat stress differentially regulate HSF1 activities in germline development.
Insulin/IGF-1 signaling and heat stress differentially regulate HSF1 activities in germline development.
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DOI：
10.1016/j.celrep.2021.109623
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发表时间：
2021-08-31
期刊：
影响因子：
8.8
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Edwards SL;Erdenebat P;Morphis AC;Kumar L;Wang L;Chamera T;Georgescu C;Wren JD;Li J
生殖系发育对养分供应和环境扰动敏感。热休克转录因子1（HSF 1）是一种调控细胞热休克反应（HSR）的关键转录因子，也参与配子发生。HSF-1（HSF-1 in C. elegans）及其在生殖系发育中的调控知之甚少。利用生长素诱导的降解决定子系统在C.通过对秀丽隐杆线虫的研究，我们发现了HSF-1在祖细胞增殖和早期减数分裂中的作用，并鉴定了HSF-1在种系发育中的紧凑但重要的转录程序。有趣的是，热应激仅诱导生殖细胞亚群中的典型HSR，但损害HSF-1在其发育靶点的结合。相反，胰岛素/胰岛素生长因子1（IGF-1）信号传导决定了生殖系发育中对HSF-1的需求，并通过抑制索马中的FOXO/FOS-16来激活生殖细胞中的HSF-1。我们认为这种非细胞自主机制将营养敏感胰岛素/IGF-1信号传导与HSF-1活化结合，以支持快速生殖细胞生长中的稳态。Edwards等人利用秀丽隐杆线虫中的生长素诱导降解，揭示了HSF-1的生殖系特异性活性，其仅在应激时诱导生殖细胞亚群中的典型热休克反应，但在发育期间与营养感应胰岛素/IGF-1信号传导偶联，以增强关键蛋白质抑制基因的表达，支持快速生殖系增殖。
Germline development is sensitive to nutrient availability and environmental perturbation. Heat shock transcription factor 1 (HSF1), a key transcription factor driving the cellular heat shock response (HSR), is also involved in gametogenesis. The precise function of HSF1 (HSF-1 in C. elegans) and its regulation in germline development are poorly understood. Using the auxin-inducible degron system in C. elegans, we uncovered a role of HSF-1 in progenitor cell proliferation and early meiosis and identified a compact but important transcriptional program of HSF-1 in germline development. Interestingly, heat stress only induces the canonical HSR in a subset of germ cells but impairs HSF-1 binding at its developmental targets. Conversely, insulin/insulin growth factor 1 (IGF-1) signaling dictates the requirement for HSF-1 in germline development and functions through repressing FOXO/DAF-16 in the soma to activate HSF-1 in germ cells. We propose that this non-cell-autonomous mechanism couples nutrient-sensing insulin/IGF-1 signaling to HSF-1 activation to support homeostasis in rapid germline growth. Using auxin-inducible degradation in Caenorhabditis elegans, Edwards et al. uncover germline-specific activities of HSF-1 that only induce the canonical heat shock response in a subset of germ cells upon stress but are coupled to nutrient-sensing insulin/IGF-1 signaling during development to enhance expression of key proteostatic genes in support of rapid germline proliferation.
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影响因子：
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期刊：
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