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

Area of Science:

• Genomics
• Developmental Biology
• Molecular Biology

Background:

• Endogenous retroviruses (ERVs) are genomic remnants with known roles in immunity and early development.
• The function of ERV-derived proteins in somatic development remains largely unexplored.

Purpose of the Study:

• To investigate the role of primate-specific ERVH48-1 in somatic development.
• To elucidate the molecular mechanisms by which ERVH48-1 influences cell fate decisions.

Main Methods:

• Analysis of ERVH48-1 function via loss-of-function studies.
• Investigation of ERVH48-1's interaction with SFRP2 and WNT/β-catenin signaling.
• Cell differentiation assays to assess mesoderm and cardiomyocyte commitment.

Main Results:

• Loss of ERVH48-1 impaired mesoderm and cardiomyocyte differentiation, promoting an ectoderm-like fate.
• ERVH48-1 targets SFRP2 for degradation, thereby activating WNT/β-catenin signaling.
• Restoring SFRP2 levels or function rescued cardiomyocyte differentiation.

Conclusions:

• ERVH48-1, a primate-specific endogenous retrovirus protein, regulates somatic development.
• ERVH48-1 modulates WNT/β-catenin signaling by degrading SFRP2, influencing cell type commitment.
• This provides novel insight into the role of ERVs in developmental processes.