Scholarlink

<p>Embryonic development demands precise coordination of transcriptional and post-transcriptional mechanisms to ensure rapid cell fate transitions, yet the molecular mechanisms by which RNA influences these transitions remain unclear. Here, we observed a global increase in mRNA stability during the blastocyst formation, which precedes rapid lineage specification. Using both in vivo and mouse totipotent blastomere-like cells (TBLCs) or extended pluripotent stem cells (EPSCs) differentiation systems, we demonstrate that this transcriptome-wide stabilization is essential for the second cell fate decision, particularly in the formation of primitive endoderm (PrE). Mechanistically, VIRMA and METTL3, the components of methyltransferase complex (MTC) establish lineage specification by stabilizing the key PrE transcription factors, including <i>Gata6</i>, via the <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) reader IGF2BP3. Knocked down of these regulatory proteins or targeted removal of m<sup>6</sup>A on <i>Gata6</i>, impacted the differentiation of PrE both in vivo and in vitro, and caused defects in blastulation and blastoid formation. Our results demonstrate that m<sup>6</sup>A-dependent post-transcriptional regulation plays a pivotal role in shaping lineage specification during peri-implantation and provided potential strategies for rescuing developmental defects.</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

Epitranscriptomic regulation of mRNA stability in pivotal transcription factors modulates the second cell fate decision

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月28日

查看全文
  • Weide Xiao,
  • Li Tang,
  • Mingli Ma,
  • Kuisheng Liu,
  • Jiaxu Lu,
  • Wenqing Ding,
  • Zhile Bai,
  • Xuelian Liu,
  • Xiaochen Kou,
  • Yanhong Zhao,
  • Hong Wang,
  • Lei Yang,
  • Shaorong Gao,
  • Yawei Gao,
  • Jun Liu

摘要

Embryonic development demands precise coordination of transcriptional and post-transcriptional mechanisms to ensure rapid cell fate transitions, yet the molecular mechanisms by which RNA influences these transitions remain unclear. Here, we observed a global increase in mRNA stability during the blastocyst formation, which precedes rapid lineage specification. Using both in vivo and mouse totipotent blastomere-like cells (TBLCs) or extended pluripotent stem cells (EPSCs) differentiation systems, we demonstrate that this transcriptome-wide stabilization is essential for the second cell fate decision, particularly in the formation of primitive endoderm (PrE). Mechanistically, VIRMA and METTL3, the components of methyltransferase complex (MTC) establish lineage specification by stabilizing the key PrE transcription factors, including Gata6, via the N6-methyladenosine (m6A) reader IGF2BP3. Knocked down of these regulatory proteins or targeted removal of m6A on Gata6, impacted the differentiation of PrE both in vivo and in vitro, and caused defects in blastulation and blastoid formation. Our results demonstrate that m6A-dependent post-transcriptional regulation plays a pivotal role in shaping lineage specification during peri-implantation and provided potential strategies for rescuing developmental defects.