Scholarlink

<p>Rebuilding human naïve pluripotency from primed stem cells is essential for generating pre-implantation epiblast-like cells, a key source for regenerative medicine. Here we present a defined, feeder-free protocol that efficiently converts primed human pluripotent stem cells (hPSCs) to a naïve-like state within 12 days. Integrated ATAC-seq, RNA-seq and miRNA-seq analyses reveal a rapid chromatin rewiring marked by increased accessibility at OCT/KLF motifs, closure at ZIC/RFX/NFκB sites, upregulation of miR-372/373 and miR-182/183, and downregulation of miR-302 and miR-363/106 clusters. Functional assays demonstrate that the inflammatory transcription factor NFκB/RELA blocks naïve induction by activating peri-implantation barrier genes, including IKBKE and VEGFR1. Conversely, enforced miR-372/373 expression accelerates conversion by directly targeting RELA. These data delineate an NFκB/RELA axis that orchestrates the epigenetic switch to human naïve pluripotency, offering a tractable framework for studying early human development and advancing cell-based therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Delicate inhibition of NFκB/RELA circuitry facilitates efficient transition towards ground-state pluripotency in human

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月7日

查看全文
  • Luqin Wang,
  • Lizhan Xiao,
  • Gaoyang Zou,
  • Huiping Mao,
  • Shihao Zhang,
  • Qiusheng Yang,
  • Chunkou Yin,
  • Jiani Wan,
  • Manish Kumar,
  • Haokaifeng Wu,
  • Haoxian Wang,
  • Xiaoli Zhang,
  • Lihua Zeng,
  • Chunhua Zhou,
  • Shengyong Yu,
  • Yi Li,
  • Lingling Zheng,
  • Yuliang Liu,
  • Baojian Liao,
  • Zhen Zhang,
  • Jing Liu

摘要

Rebuilding human naïve pluripotency from primed stem cells is essential for generating pre-implantation epiblast-like cells, a key source for regenerative medicine. Here we present a defined, feeder-free protocol that efficiently converts primed human pluripotent stem cells (hPSCs) to a naïve-like state within 12 days. Integrated ATAC-seq, RNA-seq and miRNA-seq analyses reveal a rapid chromatin rewiring marked by increased accessibility at OCT/KLF motifs, closure at ZIC/RFX/NFκB sites, upregulation of miR-372/373 and miR-182/183, and downregulation of miR-302 and miR-363/106 clusters. Functional assays demonstrate that the inflammatory transcription factor NFκB/RELA blocks naïve induction by activating peri-implantation barrier genes, including IKBKE and VEGFR1. Conversely, enforced miR-372/373 expression accelerates conversion by directly targeting RELA. These data delineate an NFκB/RELA axis that orchestrates the epigenetic switch to human naïve pluripotency, offering a tractable framework for studying early human development and advancing cell-based therapies.