PT  - JOURNAL ARTICLE
AU  - Lin Shi
AU  - Hubing Ma
AU  - Hang Zhao
AU  - Meifang Ma
AU  - Jinjun Wang
AU  - Ruiyan Kong
AU  - Zhengran Li
AU  - Rui Ma
AU  - Jian-Hua Wang
AU  - Shian Wu
AU  - Meng-qiu Dong
AU  - Zhouhua Li
TI  - The endoplasmic reticulum membrane protein complex (EMC) negatively regulates intestinal homeostasis through the Hippo signaling pathway
AID  - 10.1101/2022.01.25.477727
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.25.477727
4099  - http://biorxiv.org/content/early/2022/01/26/2022.01.25.477727.short
4100  - http://biorxiv.org/content/early/2022/01/26/2022.01.25.477727.full
AB  - 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 StatementThe authors have declared no competing interest.