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<p>Stem cells support homeostasis and injury repair of adult organs. It remains unclear when and how adult stem cells form during development. Here, we discover that incisor mesenchymal stem cells, marked by an extracellular matrix molecule <i>Smoc2</i>, establish their identity and quiescence between E14.5 and E16.5, and persist into adulthood. They support both embryonic tooth development and postnatal organ turnover. Concurrently, the incisor mesenchyme evolves from a homogenous dental papilla into a heterogeneous dental pulp consisting of a complete lineage hierarchy, which persists into adulthood. <i>Smoc2</i> and its homologous molecule <i>Smoc1</i> are indispensable for maintaining the quiescence and hierarchy of mesenchymal stem cells. They function by disrupting the binding between canonical WNT ligands and glypican, a process critical for transporting hydrophobic WNT ligands within the aqueous niche. In conclusion, mesenchymal stem cells establish their quiescence during development through autocrine extracellular matrix molecules to keep canonical WNT ligands from accessing them.</p>

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Autocrine ECM molecules establish MSC quiescence during incisor development by disrupting WNT ligand trafficking process

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月27日

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  • Zexi Chen,
  • Meilian Cai,
  • Yuling Wang,
  • Xuan Li,
  • Yongwen He,
  • Hongji Pu,
  • Juan Huang,
  • Ling Ye,
  • Ruili Yang,
  • Junjun Jing,
  • Hu Zhao

摘要

Stem cells support homeostasis and injury repair of adult organs. It remains unclear when and how adult stem cells form during development. Here, we discover that incisor mesenchymal stem cells, marked by an extracellular matrix molecule Smoc2, establish their identity and quiescence between E14.5 and E16.5, and persist into adulthood. They support both embryonic tooth development and postnatal organ turnover. Concurrently, the incisor mesenchyme evolves from a homogenous dental papilla into a heterogeneous dental pulp consisting of a complete lineage hierarchy, which persists into adulthood. Smoc2 and its homologous molecule Smoc1 are indispensable for maintaining the quiescence and hierarchy of mesenchymal stem cells. They function by disrupting the binding between canonical WNT ligands and glypican, a process critical for transporting hydrophobic WNT ligands within the aqueous niche. In conclusion, mesenchymal stem cells establish their quiescence during development through autocrine extracellular matrix molecules to keep canonical WNT ligands from accessing them.