PIWIL2 suppresses pluripotency in the male mouse germline

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 unreco

SUBMITTER: Yusuke Shiromoto 

PROVIDER: S-SCDT-10_1038-S44319-026-00965-4 | biostudies-other |

REPOSITORIES: biostudies-other