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<p>Human pluripotent stem cells (hPSCs) present considerable potential for regenerative medicine; however, the standardization and large-scale production of these cells are hindered by an incomplete understanding of the molecular mechanisms governing self-renewal. 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 in turn destabilize TGF-β1 mRNA and attenuate TGF-β signaling activity. Notably, treatment with the TGF-β agonist SRI-011381 partially rescues the self-renewal defects caused by ESRG or NPM1 knockdown. Collectively, our findings elucidate that the ESRG–NPM1–BMP4–PTBP1 axis governs hPSC self-renewal by post-transcriptionally regulating TGF-β1 mRNA stability and sustaining TGF-β signaling. This study enhances the understanding of the molecular regulatory network underlying hPSC self-renewal maintenance and validates ESRG as a promising target for improving the in vitro expansion of hPSCs.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月11日

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  • Ziling Liao,
  • Cong Zhao,
  • Lei Wang,
  • Weidong Liu,
  • Jiajing Teng,
  • Wen Xie,
  • Jinhao Ouyang,
  • Chaoyan Yao,
  • Qianping Huan,
  • Xuan Lei,
  • YuXuan Fu,
  • Bo Zhou,
  • Xingjun Jiang,
  • Caiping Ren

摘要

Human pluripotent stem cells (hPSCs) present considerable potential for regenerative medicine; however, the standardization and large-scale production of these cells are hindered by an incomplete understanding of the molecular mechanisms governing self-renewal. 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 in turn destabilize TGF-β1 mRNA and attenuate TGF-β signaling activity. Notably, treatment with the TGF-β agonist SRI-011381 partially rescues the self-renewal defects caused by ESRG or NPM1 knockdown. Collectively, our findings elucidate that the ESRG–NPM1–BMP4–PTBP1 axis governs hPSC self-renewal by post-transcriptionally regulating TGF-β1 mRNA stability and sustaining TGF-β signaling. This study enhances the understanding of the molecular regulatory network underlying hPSC self-renewal maintenance and validates ESRG as a promising target for improving the in vitro expansion of hPSCs.