{Reference Type}: Journal Article
{Title}: A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development.
{Author}: Zhang R;Wu M;Xiang D;Zhu J;Zhang Q;Zhong H;Peng Y;Wang Z;Ma G;Li G;Liu F;Ye W;Shi R;Zhou X;Babarinde IA;Su H;Chen J;Zhang X;Qin D;Hutchins AP;Pei D;Li D;
{Journal}: Cell Stem Cell
{Volume}: 31
{Issue}: 9
{Year}: 2024 Sep 5
{Factor}: 25.269
{DOI}: 10.1016/j.stem.2024.07.006
{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/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.