PIWIL2 suppresses pluripotency in the male mouse germline

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Germ cells can give rise to teratomas and express pluripotency-associated genes, yet they remain intrinsically resistant to reprogramming by Yamanaka factors. The mechanisms governing this resistance are poorly understood. Here we identify PIWIL2 as a key suppressor of pluripotency in the male germline. While spermatogonial stem cells (SSCs) normally lack SOX2 expression, Piwil2 - but not Piwil4 -deficient SSCs aberrantly express SOX2 and readily acquire pluripotency upon concurrent loss of Dmrt1 and Trp53 . piRNAs associated with the Sox2 locus are detected in embryonic gonocytes but not in SSCs. Piwil2 deficiency reduces DNA methylation at the Sox2 promoter and increases DMRT1 and the RNA-binding protein DAZL, which jointly restrict Sox2 expression. These findings reveal a previously unrecognized role of PIWIL2 in repressing germline pluripotency and underscore the importance of coordinated transcriptional and translational regulation in maintaining germ cell identity.
Funding Information
  • AMED (17933225)
  • AMED (JP24zf0127011)
  • MEXT (26H02453)
  • MEXT (24H02045)
  • MEXT (23H00399)
  • MEXT (23K20043)
  • MEXT (24K21291)
  • MEXT (23K27727)
  • MEXT (26K23942)
  • Takeda Science Foundation

This publication has 59 references indexed in Scilit: