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

Autor:	Zhang R; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China., Wu M; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China., Xiang D; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Hong Kong Institute of Science & Innovation, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China., Zhu J; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Hong Kong Institute of Science & Innovation, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China., Zhang Q; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China., Zhong H; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Hong Kong Institute of Science & Innovation, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China., Peng Y; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China., Wang Z; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China., Ma G; Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China., Li G; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China., Liu F; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China; Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau 999078, China., Ye W; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China., Shi R; University of Chinese Academy of Sciences, Beijing 100049, China., Zhou X; Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China., Babarinde IA; Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China., Su H; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China., Chen J; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Hong Kong Institute of Science & Innovation, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China., Zhang X; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Hong Kong Institute of Science & Innovation, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: zhang_xiaofei@gibh.ac.cn., Qin D; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China. Electronic address: qin_dajiang@gzhmu.edu.cn., Hutchins AP; Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: andrewh@sustech.edu.cn., Pei D; Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou 310024, China. Electronic address: peiduanqing@westlake.edu.cn., Li D; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China. Electronic address: lidongwei@gzhmu.edu.cn.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Sep 05; Vol. 31 (9), pp. 1298-1314.e8. Date of Electronic Publication: 2024 Aug 14.
DOI:	10.1016/j.stem.2024.07.006
Abstrakt:	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). 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/β-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/β-catenin signaling and cell type commitment in somatic development. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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