Activation of the EGFR/MAPK pathway drives transdifferentiation of quiescent niche cells to stem cells in the Drosophila testis niche.
Activation of the EGFR/MAPK pathway drives transdifferentiation of quiescent niche cells to stem cells in the Drosophila testis niche.
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DOI：
10.7554/elife.70810
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发表时间：
2022-04-25
期刊：
影响因子：
7.7
通讯作者：
Matunis, Erika L.
中科院分区：
文献类型：
--
作者：
Greenspan, Leah J.;de Cuevas, Margaret;Le, Kathy H.;Viveiros, Jennifer M.;Matunis, Erika L.
成体干细胞维持在生态位、调节其自我更新和分化的特殊微环境中。在成年果蝇睾丸干细胞生态位中，体细胞中枢细胞产生调节相邻生殖干细胞（GSC）和体细胞囊肿干细胞（CySC）的信号。 Hub 细胞通常处于静止状态，但在 CySC 完全基因消融后，它们可以增殖并转分化为新的 CySC。在这里，我们发现 CySC 消融后，中枢细胞中的表皮生长因子受体 (EGFR) 信号传导上调，并且 EGFR 信号传导减少抑制了睾丸从消融中恢复的能力。此外，中枢细胞中 EGFR 通路的激活足以诱导其增殖并转分化为 CySC。我们提出，成体囊肿细胞通常需要的 EGFR 信号传导在成体中枢细胞中被主动抑制以维持其命运，但在 CySC 消融后被重新用于驱动干细胞再生。
Adult stem cells are maintained in niches, specialized microenvironments that regulate their self-renewal and differentiation. In the adult Drosophila testis stem cell niche, somatic hub cells produce signals that regulate adjacent germline stem cells (GSCs) and somatic cyst stem cells (CySCs). Hub cells are normally quiescent, but after complete genetic ablation of CySCs, they can proliferate and transdifferentiate into new CySCs. Here we find that Epidermal growth factor receptor (EGFR) signaling is upregulated in hub cells after CySC ablation and that the ability of testes to recover from ablation is inhibited by reduced EGFR signaling. In addition, activation of the EGFR pathway in hub cells is sufficient to induce their proliferation and transdifferentiation into CySCs. We propose that EGFR signaling, which is normally required in adult cyst cells, is actively inhibited in adult hub cells to maintain their fate but is repurposed to drive stem cell regeneration after CySC ablation.