增殖干细胞通过分泌激活素抑制剂卵泡抑素来维持其龛位的静止状态。
Proliferative stem cells maintain quiescence of their niche by secreting the Activin inhibitor Follistatin.
机构信息
Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Centro Andaluz de Biología del Desarrollo, CSIC/Universidad Pablo de Olavide/JA, Carretera de Utrera km 1, 41013 Sevilla, Spain.
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
出版信息
Dev Cell. 2021 Aug 23;56(16):2284-2294.e6. doi: 10.1016/j.devcel.2021.07.010. Epub 2021 Aug 6.
Aging causes stem cell dysfunction as a result of extrinsic and intrinsic changes. Decreased function of the stem cell niche is an important contributor to this dysfunction. We use the Drosophila testis to investigate what factors maintain niche cells. The testis niche comprises quiescent "hub" cells and supports two mitotic stem cell pools: germline stem cells and somatic cyst stem cells (CySCs). We identify the cell-cycle-responsive Dp/E2f1 transcription factor as a crucial non-autonomous regulator required in CySCs to maintain hub cell quiescence. Dp/E2f1 inhibits local Activin ligands through production of the Activin antagonist Follistatin (Fs). Inactivation of Dp/E2f1 or Fs in CySCs or promoting Activin receptor signaling in hub cells causes transdifferentiation of hub cells into fully functional CySCs. This Activin-dependent communication between CySCs and hub regulates the physiological decay of the niche with age and demonstrates that hub cell quiescence results from signals from surrounding stem cells.
衰老会导致干细胞功能障碍，这是由外在和内在变化引起的。干细胞龛的功能下降是导致这种功能障碍的一个重要因素。我们使用果蝇的睾丸来研究维持龛细胞的因素。睾丸龛由静止的“中心”细胞组成，支持两个有丝分裂的干细胞池：生殖干细胞和体腔干细胞（CySCs）。我们确定细胞周期反应性 Dp/E2f1 转录因子是 CySCs 中维持中心细胞静止所必需的关键非自主性调节因子。Dp/E2f1 通过产生激活素拮抗剂 Follistatin（Fs）来抑制局部激活素配体。在 CySCs 中失活 Dp/E2f1 或 Fs 或促进中心细胞中的激活素受体信号会导致中心细胞转化为完全功能性的 CySCs。CySCs 和中心细胞之间的这种依赖激活素的通讯调节了随着年龄增长而导致的龛的生理衰退，并表明中心细胞的静止是由周围干细胞的信号引起的。
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