Histone H1 defect in escort cells triggers germline tumor in Drosophila ovary
Histone H1 defect in escort cells triggers germline tumor in Drosophila ovary
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护送细胞中的组蛋白 H1 缺陷引发果蝇卵巢生殖系肿瘤
DOI：
10.1016/j.ydbio.2017.02.012
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发表时间：
2017
影响因子：
2.7
通讯作者：
Jian-Quan Ni
中科院分区：
文献类型：
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作者：
Zhihao Yang;Jin Sun;Yuzhao Hu;Fang Wang;Xia Wang;Huan-Huan Qiao;Jiang Xu;Decai Mao;Xingjie Ren;Li-Xia Pan;Rong-Gang Xu;Bo-Wen Xu;Yifan Zhang;Haiyi Li;Wei Miao;Yanhui Hu;Zhijie Chang;Dong Wang;Haitao Li;Zai Chang;Lu-Ping Liu;Qingfei Liu;Jian-Quan Ni
果蝇是研究干细胞生物学的最佳模型系统之一。我们先前已经确定了组蛋白H1在生殖系干细胞（GSC）维持中的自主作用。在这里，我们发现，组蛋白H1在护送细胞（EC）的耗竭导致增加的spectrosome包含细胞（SCC），卵巢肿瘤样表型。进一步的分析表明，在这些SCC细胞中，Dpp通路被过度激活，而bamis的表达减弱。在H1缺失的EC中，转座子活性和DNA损伤均显著增加，随后EC凋亡，这与H1在其他体细胞中的作用一致。令人惊讶的是，H1缺失的EC获得了包括dpp表达在内的帽细胞特征，并且由此产生的异常Dpp水平抑制了SCC的进一步分化。最有趣的是，H1和dppin ECs的双敲低可以将SCC的数量减少到正常水平，表明EC分泌的额外Dpp有助于生殖系肿瘤。综上所述，我们的研究结果表明，组蛋白H1是一个重要的表观遗传因子在控制EC的特点和生殖系肿瘤的关键抑制因子。
Drosophilaovary is recognized as one of the best model systems to study stem cell biology invivo. We had previously identified an autonomous role of the histone H1 in germline stem cell (GSC) maintenance. Here, we found that histone H1 depletion in escort cells (ECs) resulted in an increase of spectrosome-containing cells (SCCs), an ovary tumor-like phenotype. Further analysis showed that the Dpp pathway is excessively activated in these SCC cells, while the expression ofbamis attenuated. In the H1-depleted ECs, both transposon activity and DNA damage had increased dramatically, followed by EC apoptosis, which is consistent with the role of H1 in other somatic cells. Surprisingly, H1-depleted ECs acquired cap cell characteristics includingdppexpression, and the resulting abnormal Dpp level inhibits SCC further differentiation. Most interestingly, double knockdown of H1 anddppin ECs can reduce the number of SCCs to the normal level, indicating that the additional Dpp secreted by ECs contributes to the germline tumor. Taken together, our findings indicate that histone H1 is an important epigenetic factor in controlling EC characteristics and a key suppressor of germline tumor.