Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Cell Stem Cell. 2010 Nov 5;7(5):581-92. doi: 10.1016/j.stem.2010.10.001.
Steroid hormones are known systemic regulators of multiple normal and cancerous tissues; however, whether or how they impact the fate and function of adult stem cells is unclear. In the Drosophila ovary, insulin signals modulate the proliferation and self-renewal of germline stem cells (GSCs), yet despite evidence that additional systemic factors control GSC activity, these have remained largely unknown. Here, we report that ecdysone, a steroid hormone structurally related to mammalian sex steroids, directly regulates adult GSC proliferation and self-renewal independently of insulin signaling. Ecdysone controls GSCs through a functional interaction with the chromatin remodeling factors ISWI, an intrinsic epigenetic factor required for GSC fate and activity, and Nurf301, the largest subunit of the ISWI-containing NURF chromatin remodeling complex. Our findings support a link between systemic steroid hormones and the intrinsic chromatin remodeling machinery as a potential mechanism to promote broad transcriptional programs required for adult stem cell self-renewal.
类固醇激素是多种正常组织和癌变组织的系统调节因子;然而,它们是否以及如何影响成体干细胞的命运和功能尚不清楚。在果蝇卵巢中,胰岛素信号调节生殖干细胞(GSCs)的增殖和自我更新,尽管有证据表明其他系统因素控制 GSC 的活性,但这些因素在很大程度上仍然未知。在这里,我们报告说,蜕皮激素是一种与哺乳动物性激素在结构上相关的甾体激素,可独立于胰岛素信号直接调节成体 GSC 的增殖和自我更新。蜕皮激素通过与染色质重塑因子 ISWI 的功能相互作用来控制 GSCs,ISWI 是 GSC 命运和活性所必需的内在表观遗传因子,以及 Nurf301,它是包含 ISWI 的 NURF 染色质重塑复合物的最大亚基。我们的研究结果支持系统类固醇激素与内在染色质重塑机制之间的联系,这可能是促进成体干细胞自我更新所需的广泛转录程序的潜在机制。