ESRG maintains human pluripotent stem cell self-renewal by binding NPM1 to regulate BMP4 protein and TGF-β signaling pathway

The long non-coding RNA ESRG is integral to maintaining hPSC self-renewal, with its depletion leading to reduced levels of nucleophosmin 1 (NPM1) protein, thereby compromising the self-renewal capacity of hPSCs.

Mechanistically, ESRG physically interacts with NPM1, and a reduction in ESRG/NPM1 expression results in elevated bone morphogenetic protein 4 (BMP4) levels and decreased polypyrimidine tract-binding protein 1 (PTBP1) levels, which subsequently suppress TGF-β signaling by destabilizing TGF-β1 mRNA. Notably, treatment with the TGF-β activator SRI-011381 partially mitigates the self-renewal defects induced by ESRG or NPM1 downregulation.