RT Journal Article SR Electronic T1 The endoplasmic reticulum membrane protein complex (EMC) negatively regulates intestinal homeostasis through the Hippo signaling pathway JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.01.25.477727 DO 10.1101/2022.01.25.477727 A1 Lin Shi A1 Hubing Ma A1 Hang Zhao A1 Meifang Ma A1 Jinjun Wang A1 Ruiyan Kong A1 Zhengran Li A1 Rui Ma A1 Jian-Hua Wang A1 Shian Wu A1 Meng-qiu Dong A1 Zhouhua Li YR 2022 UL http://biorxiv.org/content/early/2022/01/26/2022.01.25.477727.abstract 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.