Proliferative stem cells maintain quiescence of their niche by secreting the Activin inhibitor Follistatin.
Proliferative stem cells maintain quiescence of their niche by secreting the Activin inhibitor Follistatin.
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DOI：
10.1016/j.devcel.2021.07.010
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发表时间：
2021-08-23
影响因子：
11.8
通讯作者：
Bach EA
中科院分区：
文献类型：
--
作者：
Herrera SC;Sainz de la Maza D;Grmai L;Margolis S;Plessel R;Burel M;O'Connor M;Amoyel M;Bach EA
由于外在和内在的变化，衰老导致干细胞功能障碍。干细胞生态位功能的降低是导致这种功能障碍的重要因素。我们使用果蝇睾丸来研究维持生态位细胞的因素。睾丸生态位由静止的“中枢”细胞组成，并支持两个有丝分裂干细胞池：种系干细胞和体细胞囊肿干细胞（CySCs）。我们发现细胞周期响应的Dp/E2f1转录因子是CySCs维持中心细胞静止所需的关键非自主调节因子。Dp/E2f1通过产生激活素拮抗剂Follistatin （Fs）抑制局部激活素配体。CySCs中的Dp/E2f1或Fs失活或促进hub细胞中的Activin受体信号传导可导致hub细胞转分化为功能完整的CySCs。CySCs和hub之间的这种依赖激活素的通信调节了生态位随年龄增长的生理衰退，并表明hub细胞的静止是由周围干细胞的信号引起的。Dp/E2f1在干细胞中是非自主维持生态位静止所必需的Dp/E2f1通过激活素拮抗剂Fs促进生态位静止，激活素信号在生态位细胞中引起向功能性干细胞的转分化，干细胞中的Fs调节生态位随年龄的生理衰变，干细胞如何支持生态位仍然很大程度上未知。Herrera等人发现睾丸干细胞通过分泌卵泡素（一种激活素拮抗剂）来维持生态位静止。干细胞中Follistatin的缺失或生态位细胞中激活素信号的获得会导致生态位向干细胞的转分化，这一过程是衰老过程中生态位衰退的基础。
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. Dp/E2f1 is required in stem cells to non-autonomously maintain niche quiescence Dp/E2f1 promotes niche quiescence through Fs, an Activin antagonist Activin signaling in niche cells causes transdifferentiation into functional stem cells Fs in stem cells regulates the physiological decay of the niche with age How stem cells support niches remains largely unknown. Herrera et al. show that testicular stem cells maintain niche quiescence by secreting Follistatin, an Activin antagonist. Loss of Follistatin in stem cells or gain of Activin signaling in niche cells causes niche-to-stem-cell transdifferentiation, and this process underlies niche decay during aging.
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影响因子：
4.6
作者：
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通讯作者：
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影响因子：
8.8
作者：
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DOI：
10.1126/stke.2202004pl6
发表时间：
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期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1003462107
发表时间：
2010-08-10
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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