Steroid signaling promotes stem cell maintenance in the Drosophila testis.
Steroid signaling promotes stem cell maintenance in the Drosophila testis.
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DOI：
10.1016/j.ydbio.2014.07.016
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发表时间：
2014-10-01
影响因子：
2.7
通讯作者：
Matunis, Erika L.
中科院分区：
文献类型：
--
作者：
Li, Yijie;Ma, Qing;Cherry, Christopher M.;Matunis, Erika L.
通过局部信号对干细胞的调节被深入研究，但对激素信号对干细胞的影响知之甚少。在果蝇中，主要的类固醇二十羟蜕皮激素（20 E）调节卵巢生殖系干细胞（GSC），但被认为是睾丸GSC维持。雄性GSC驻留在由体细胞中枢细胞和相邻的囊肿干细胞（CySC）产生的微环境（小生境）中。在这里，我们表明，从成年男性的蜕皮激素受体（EcR）或其异二聚体伴侣ultraspiracle（USP）的显性负形式的耗尽20 E导致GSC和CySC的损失，这是由20 E喂养拯救，揭示了干细胞维持中对20 E的需求。EcR和USP在CySC谱系中表达、激活并自主需要以促进CySC维持，下游基因ftz-f1和E75也是如此。相反，GSC非自主地需要蜕皮激素信号传导。EcR的整体失活增加了睾丸中的细胞死亡，这是由CySC谱系中EcR-B2的表达拯救的，表明蜕皮激素信号传导主要通过特异性受体亚型支持干细胞活力。最后，EcR基因相互作用的cDNAF染色质重塑复合物，我们以前显示维持CySC。因此，尽管男性的20 E水平低于女性，但蜕皮激素信号通过不同的细胞类型和效应器发挥作用，以确保卵巢和睾丸干细胞的维持。
Stem cell regulation by local signals is intensely studied, but less is known about the effects of hormonal signals on stem cells. In Drosophila, the primary steroid twenty-hydroxyecdysone (20E) regulates ovarian germline stem cells (GSCs) but was considered dispensable for testis GSC maintenance. Male GSCs reside in a microenvironment (niche) generated by somatic hub cells and adjacent cyst stem cells (CySCs). Here, we show that depletion of 20E from adult males by overexpressing a dominant negative form of the Ecdysone receptor (EcR) or its heterodimeric partner ultraspiracle (usp) causes GSC and CySC loss that is rescued by 20E feeding, uncovering a requirement for 20E in stem cell maintenance. EcR and USP are expressed, activated and autonomously required in the CySC lineage to promote CySC maintenance, as are downstream genes ftz-f1 and E75. In contrast, GSCs non-autonomously require ecdysone signaling. Global inactivation of EcR increases cell death in the testis that is rescued by expression of EcR-B2 in the CySC lineage, indicating that ecdysone signaling supports stem cell viability primarily through a specific receptor isoform. Finally, EcR genetically interacts with the NURF chromatin-remodeling complex, which we previously showed maintains CySCs. Thus, although 20E levels are lower in males than females, ecdysone signaling acts through distinct cell types and effectors to ensure both ovarian and testis stem cell maintenance.
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影响因子：
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