A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development

Zhang, Ran1,3; Wu, Menghua1; Xiang, Dan4,7; Zhu, Jieying4; Zhang, Qi1; Zhong, Hui4; Peng, Yuling1; Wang, Zhenhua1; Ma, Gang5; Li, Guihuan1; Liu, Fengping1,8; Ye, Weipeng1; Shi, Ruona7; Zhou, Xuemeng5; Babarinde, Isaac A.5; Su, Huanxing3; Chen, Jiekai4; Zhang, Xiaofei1,4,7; Qin, Dajiang1,2; Hutchins, Andrew P.5; Pei, Duanqing6; Li, Dongwei1

2024-09-05

10.1016/j.stem.2024.07.006

CELL STEM CELL   影响因子和分区

1934-5909

1875-9777

Endogenous retroviruses (ERVs) occupy a significant part of the human genome, with some encoding proteins that influence the immune system or regulate cell-cell fusion in early extra-embryonic development. However, whether ERV-derived proteins regulate somatic development is unknown. Here, we report a somatic developmental function for the primate-specific ERVH48-1 (SUPYN/Suppressyn). SUPYN /Suppressyn). ERVH48-1 encodes a fragment of a viral envelope that is expressed during early embryonic development. Loss of ERVH48-1 led to impaired mesoderm and cardiomyocyte commitment and diverted cells to an ectoderm-like fate. Mechanistically, ERVH48-1 is localized to sub-cellular membrane compartments through a functional N-terminal signal peptide and binds to the WNT antagonist SFRP2 to promote its polyubiquitination and degradation, thus limiting SFRP2 secretion and blocking repression of WNT/b-catenin signaling. Knockdown of SFRP2 or expression of a chimeric SFRP2 with the ERVH48-1 signal peptide rescued cardiomyocyte differentiation. This study demonstrates how ERVH48-1 modulates WNT/b-catenin signaling and cell type commitment in somatic development.

SCI

英语

通讯

National Natural Science Foundation of China["92068201","32270574","31830060","32270597"] ; National Key R&D Program of China[2019YFA0110200] ; Youth Innovation Promotion of the Chinese Academy of Sciences[2019348] ; Guangdong Pearl River Talents Program[2019QN01Y051] ; Guangzhou Key Laboratory of Biological Targeting Diagnosis and Therapy[202201020379] ; Key Laboratory of Guangdong Higher Education Institutes[2021KSYS009] ; China Postdoctoral Science Foundation[2022M710901] ; High-level Hospital Construction Project[DFJHBF202110] ; Guangdong Basic and Applied Basic Research Foundation[2022A1515110201] ; Science Technology and Innovation Commission of Shenzhen[RCBS20221008093109033] ; null[2023A03J0045]

Cell Biology

Cell & Tissue Engineering ; Cell Biology

WOS:001317251100001

CELL PRESS

Web of Science

1.Guangzhou Med Univ, Affiliated Hosp 5, Therapy & Rehabil Guangdong Higher Educ Inst, Key Lab Biol Targeting Diag, Guangzhou 510799, Peoples R China
2.Chinese Acad Sci, Hong Kong Inst Sci & Innovat, Ctr Regenerat Med & Hlth, Hong Kong, Peoples R China
3.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
4.Hong Kong Inst Sci & Innovat, Guangzhou Inst Biomed & Hlth, GIBH HKU Guangdong Hong Kong Stem Cell & Regenerat, CAS Key Lab Regenerat Biol,Guangdong Prov Key Lab, Guangzhou 510530, Guangdong, Peoples R China
5.Southern Univ Sci & Technol, Sch Life Sci, Dept Syst Biol, Shenzhen 518055, Peoples R China
6.Westlake Univ, Sch Life Sci, Lab Cell Fate Control, Hangzhou 310024, Peoples R China
7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
8.Macau Univ Sci & Technol, Fac Med, Macau 999078, Peoples R China

Zhang, Ran,Wu, Menghua,Xiang, Dan,et al. A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development[J]. CELL STEM CELL,2024,31(9).

Zhang, Ran.,Wu, Menghua.,Xiang, Dan.,Zhu, Jieying.,Zhang, Qi.,...&Li, Dongwei.(2024).A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development.CELL STEM CELL,31(9).

Zhang, Ran,et al."A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development".CELL STEM CELL 31.9(2024).