ClC-c regulates the proliferation of intestinal stem cells via the EGFR signalling pathway in Drosophila.
ClC-c regulates the proliferation of intestinal stem cells via the EGFR signalling pathway in Drosophila.
复制标题
ClC-c 通过 EGFR 信号通路调节果蝇肠道干细胞的增殖。
DOI：
10.1111/cpr.13173
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发表时间：
2022-01
影响因子：
8.5
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Huang J;Sheng X;Zhuo Z;Xiao D;Wu K;Wan G;Chen H
成体干细胞在静止和活跃状态之间保持微妙的平衡，这对组织的稳态至关重要。尽管已经报道了许多调节上皮干细胞的信号传导途径，但许多调节剂仍然未被确定。使用果蝇产生组织特异性基因敲低和基因敲除。使用qRT-PCR评估相对mRNA水平。免疫荧光用于确定蛋白定位和表达模式。克隆分析用于观察表型。使用RNA-seq筛选下游机制。在这里，我们报告了氯离子通道家族的一个成员，ClC-c，它在果蝇肠道干/祖细胞中特异性表达，并在生理条件下和组织损伤时调节肠道干细胞（ISC）增殖。从机制上讲，我们发现肠干/祖细胞中ClC-c耗竭诱导的ISC损失是由于EGFR信号通路的抑制。我们的研究结果揭示了ClC-c在调节干细胞维持和增殖中的ISC特异性功能，从而为氯通道家族，ISC增殖和组织稳态之间的功能联系提供了新的见解。我们的研究结果表明，ClC‐c（果蝇ClC‐3的同源基因）在成体肠干细胞中表达，并且在体内平衡期间和组织损伤后对增殖至关重要。这项研究表明，ClC-c通过EGFR信号通路调节ISC增殖。
Adult stem cells uphold a delicate balance between quiescent and active states, which is crucial for tissue homeostasis. Whereas many signalling pathways that regulate epithelial stem cells have been reported, many regulators remain unidentified. Flies were used to generate tissue‐specific gene knockdown and gene knockout. qRT‐PCR was used to assess the relative mRNA levels. Immunofluorescence was used to determine protein localization and expression patterns. Clonal analyses were used to observe the phenotype. RNA‐seq was used to screen downstream mechanisms. Here, we report a member of the chloride channel family, ClC‐c, which is specifically expressed in Drosophila intestinal stem/progenitor cells and regulates intestinal stem cell (ISC) proliferation under physiological conditions and upon tissue damage. Mechanistically, we found that the ISC loss induced by the depletion of ClC‐c in intestinal stem/progenitor cells is due to inhibition of the EGFR signalling pathway. Our findings reveal an ISC‐specific function of ClC‐c in regulating stem cell maintenance and proliferation, thereby providing new insights into the functional links among the chloride channel family, ISC proliferation and tissue homeostasis. Our findings show that ClC‐c (the homologous gene of ClC‐3 in Drosophila) is expressed in adult intestinal stem cells and is essential for proliferation during homeostasis and after tissue damage. This study demonstrates that ClC‐c regulates ISC proliferation through the EGFR signalling pathway.
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