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ClC-c 通过 EGFR 信号通路调控果蝇肠道干细胞的增殖。

ClC-c regulates the proliferation of intestinal stem cells via the EGFR signalling pathway in Drosophila.

机构信息

Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.

Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Cell Prolif. 2022 Jan;55(1):e13173. doi: 10.1111/cpr.13173. Epub 2021 Dec 24.

DOI:10.1111/cpr.13173
PMID:34952996
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8780901/
Abstract

OBJECTIVES

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

成体干细胞在静息和活跃状态之间维持着微妙的平衡，这对于组织稳态至关重要。虽然已经报道了许多调节上皮干细胞的信号通路，但仍有许多调节剂尚未被鉴定。

材料和方法

利用果蝇生成组织特异性基因敲低和基因敲除。采用 qRT-PCR 评估相对 mRNA 水平。免疫荧光用于确定蛋白质定位和表达模式。克隆分析用于观察表型。RNA-seq 用于筛选下游机制。

结果

本研究报告了氯离子通道家族的一个成员 ClC-c，它在果蝇肠道干细胞/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）的增殖。在机制上，我们发现 ClC-c 在肠道干细胞/祖细胞中的耗竭诱导的 ISC 损失是由于 EGFR 信号通路的抑制。

结论

本研究揭示了 ClC-c 在调节干细胞维持和增殖方面的 ISC 特异性功能，从而为氯离子通道家族、ISC 增殖和组织稳态之间的功能联系提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/1b655a0237fb/CPR-55-e13173-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/004c5ccf59f2/CPR-55-e13173-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/9b7df93c9168/CPR-55-e13173-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/2c3265e97faa/CPR-55-e13173-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/a3968e0bc0ed/CPR-55-e13173-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/2f8b4e6a1ed8/CPR-55-e13173-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/ab28418336f0/CPR-55-e13173-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/1b655a0237fb/CPR-55-e13173-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/004c5ccf59f2/CPR-55-e13173-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/9b7df93c9168/CPR-55-e13173-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/2c3265e97faa/CPR-55-e13173-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/a3968e0bc0ed/CPR-55-e13173-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/2f8b4e6a1ed8/CPR-55-e13173-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/ab28418336f0/CPR-55-e13173-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2324/8780901/1b655a0237fb/CPR-55-e13173-g008.jpg

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2
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J Cell Sci. 2020 Oct 12;133(19):jcs246199. doi: 10.1242/jcs.246199.
3
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Cell Rep. 2020 May 26;31(8):107683. doi: 10.1016/j.celrep.2020.107683.
4
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Dev Cell. 2020 Apr 20;53(2):169-184.e11. doi: 10.1016/j.devcel.2020.03.002. Epub 2020 Apr 2.
5
Targeting of early endosomes by autophagy facilitates EGFR recycling and signalling.自噬靶向早期内体促进 EGFR 循环和信号转导。
EMBO Rep. 2019 Oct 4;20(10):e47734. doi: 10.15252/embr.201947734. Epub 2019 Aug 26.
6
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7
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8
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9
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