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The endoplasmic reticulum membrane protein complex (EMC) negatively regulates intestinal homeostasis through the Hippo signaling pathway

Lin Shi, Hubing Ma, Hang Zhao, Meifang Ma, Jinjun Wang, Ruiyan Kong, View ORCID ProfileZhengran Li, Rui Ma, Jian-Hua Wang, Shian Wu, View ORCID ProfileMeng-qiu Dong, Zhouhua Li
doi: https://doi.org/10.1101/2022.01.25.477727
Lin Shi
1College of Life Sciences, Capital Normal University, Beijing 100048, China
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Hubing Ma
1College of Life Sciences, Capital Normal University, Beijing 100048, China
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Hang Zhao
1College of Life Sciences, Capital Normal University, Beijing 100048, China
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Meifang Ma
1College of Life Sciences, Capital Normal University, Beijing 100048, China
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Jinjun Wang
1College of Life Sciences, Capital Normal University, Beijing 100048, China
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Ruiyan Kong
1College of Life Sciences, Capital Normal University, Beijing 100048, China
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Zhengran Li
1College of Life Sciences, Capital Normal University, Beijing 100048, China
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  • ORCID record for Zhengran Li
Rui Ma
2Department of Neurology, Capital Medical University, Beijing 100053, China
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Jian-Hua Wang
3National Institute of Biological Sciences, Beijing 102206, China
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Shian Wu
4College of Life Sciences, Nankai University, Tianjin 300071, China
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Meng-qiu Dong
3National Institute of Biological Sciences, Beijing 102206, China
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Zhouhua Li
1College of Life Sciences, Capital Normal University, Beijing 100048, China
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  • For correspondence: zhli@cnu.edu.cn
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Abstract

Disruption of tissue homeostasis often results in many diseases. Balanced control of stem cell proliferation and differentiation underlines tissue homeostasis. However, how endogenous factors influence the proliferation and differentiation of intestinal stem cells (ISCs) under physiological conditions remains not fully understood. Here, we find that the endoplasmic reticulum membrane protein complex (EMC) negatively regulates ISC proliferation in adult Drosophila midgut. Compromising EMC function in progenitors leads to excessive ISC proliferation and intestinal homeostasis disruption. Mechanistically, the EMC complex associates with and stabilizes Hippo (Hpo), the key component of the Hpo signaling pathway. In the absence of the EMC complex, Yki (Yorkie) is activated to promote ISC proliferation. Furthermore, the role of the EMC complex in stem cell proliferation control is evolutionarily conserved. Thus, our study uncovers the molecular mechanism of the EMC complex in controlling stem cell proliferation. Our results provide new insight into the underlying mechanisms of how stem cell proliferation is properly controlled under physiological conditions.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 26, 2022.
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The endoplasmic reticulum membrane protein complex (EMC) negatively regulates intestinal homeostasis through the Hippo signaling pathway
Lin Shi, Hubing Ma, Hang Zhao, Meifang Ma, Jinjun Wang, Ruiyan Kong, Zhengran Li, Rui Ma, Jian-Hua Wang, Shian Wu, Meng-qiu Dong, Zhouhua Li
bioRxiv 2022.01.25.477727; doi: https://doi.org/10.1101/2022.01.25.477727
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The endoplasmic reticulum membrane protein complex (EMC) negatively regulates intestinal homeostasis through the Hippo signaling pathway
Lin Shi, Hubing Ma, Hang Zhao, Meifang Ma, Jinjun Wang, Ruiyan Kong, Zhengran Li, Rui Ma, Jian-Hua Wang, Shian Wu, Meng-qiu Dong, Zhouhua Li
bioRxiv 2022.01.25.477727; doi: https://doi.org/10.1101/2022.01.25.477727

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