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<p>The nuclear matrix, a proteinaceous gel composed of proteins and RNA, is an important nuclear structure that supports chromatin architecture, but its role in human pluripotent stem cells (hPSCs) has not been described. Here we show that by disrupting heterogeneous nuclear ribonucleoprotein U (HNRNPU) or the nuclear matrix protein, Matrin-3, primed hPSCs adopted features of the naive pluripotent state, including morphology and upregulation of naive-specific marker genes. We demonstrate that <i>HNRNPU</i> depletion leads to increased chromatin accessibility, reduced DNA contacts and increased nuclear size. Mechanistically, HNRNPU acts as a transcriptional co-factor that anchors promoters of primed-specific genes to the nuclear matrix with POLII to promote their expression and their RNA stability. Overall, HNRNPU promotes cell-type stability and when reduced promotes conversion to earlier embryonic states.</p>

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The nuclear matrix stabilizes primed-specific genes in human pluripotent stem cells

  • 期刊论文

  • 发表日期：

    2025年1月9日

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  • Gang Ma,
  • Xiuling Fu,
  • Lulu Zhou,
  • Isaac A. Babarinde,
  • Liyang Shi,
  • Wenting Yang,
  • Jiao Chen,
  • Zhen Xiao,
  • Yu Qiao,
  • Lisha Ma,
  • Yuhao Ou,
  • Yuhao Li,
  • Chen Chang,
  • Boping Deng,
  • Ran Zhang,
  • Li Sun,
  • Guoqing Tong,
  • Dongwei Li,
  • Yiming Li,
  • Andrew P. Hutchins

摘要

The nuclear matrix, a proteinaceous gel composed of proteins and RNA, is an important nuclear structure that supports chromatin architecture, but its role in human pluripotent stem cells (hPSCs) has not been described. Here we show that by disrupting heterogeneous nuclear ribonucleoprotein U (HNRNPU) or the nuclear matrix protein, Matrin-3, primed hPSCs adopted features of the naive pluripotent state, including morphology and upregulation of naive-specific marker genes. We demonstrate that HNRNPU depletion leads to increased chromatin accessibility, reduced DNA contacts and increased nuclear size. Mechanistically, HNRNPU acts as a transcriptional co-factor that anchors promoters of primed-specific genes to the nuclear matrix with POLII to promote their expression and their RNA stability. Overall, HNRNPU promotes cell-type stability and when reduced promotes conversion to earlier embryonic states.