A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development.
Cell Stem Cell
; 31(9): 1298-1314.e8, 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-39146934
ABSTRACT
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/ß-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/ß-catenin signaling and cell type commitment in somatic development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Retrovirus Endógenos
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Miócitos Cardíacos
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Via de Sinalização Wnt
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Proteínas de Membrana
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Estados Unidos