Upadhyay Maitreyi, Martino Cortez Yesenia, Wong-Deyrup SiuWah, Tavares Leticia, Schowalter Sean, Flora Pooja, Hill Corinne, Nasrallah Mohamad Ali, Chittur Sridar, Rangan Prashanth
Department of Biological Sciences/RNA Institute, University at Albany SUNY, Albany, New York, United States of America.
NYU Langone Medical Center, New York, New York, United States of America.
PLoS Genet. 2016 Mar 28;12(3):e1005918. doi: 10.1371/journal.pgen.1005918. eCollection 2016 Mar.
Germline stem cell (GSC) self-renewal and differentiation are required for the sustained production of gametes. GSC differentiation in Drosophila oogenesis requires expression of the histone methyltransferase dSETDB1 by the somatic niche, however its function in this process is unknown. Here, we show that dSETDB1 is required for the expression of a Wnt ligand, Drosophila Wingless type mouse mammary virus integration site number 4 (dWnt4) in the somatic niche. dWnt4 signaling acts on the somatic niche cells to facilitate their encapsulation of the GSC daughter, which serves as a differentiation cue. dSETDB1 is known to repress transposable elements (TEs) to maintain genome integrity. Unexpectedly, we found that independent upregulation of TEs also downregulated dWnt4, leading to GSC differentiation defects. This suggests that dWnt4 expression is sensitive to the presence of TEs. Together our results reveal a chromatin-transposon-Wnt signaling axis that regulates stem cell fate.
生殖系干细胞(GSC)的自我更新和分化是持续产生配子所必需的。在果蝇卵子发生过程中,GSC分化需要体细胞微环境表达组蛋白甲基转移酶dSETDB1,然而其在这一过程中的功能尚不清楚。在这里,我们表明dSETDB1是体细胞微环境中Wnt配体——果蝇无翅型小鼠乳腺病毒整合位点4(dWnt4)表达所必需的。dWnt4信号作用于体细胞微环境细胞,促进它们对GSC子代的包裹,这作为一种分化信号。已知dSETDB1可抑制转座元件(TEs)以维持基因组完整性。出乎意料的是,我们发现TEs的独立上调也会下调dWnt4,导致GSC分化缺陷。这表明dWnt4的表达对TEs的存在敏感。我们的结果共同揭示了一个调节干细胞命运的染色质-转座子-Wnt信号轴。