Zhao Hu, Feng Jifan, Ho Thach-Vu, Grimes Weston, Urata Mark, Chai Yang
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103 Los Angeles, California 90033, USA.
Nat Cell Biol. 2015 Apr;17(4):386-96. doi: 10.1038/ncb3139. Epub 2015 Mar 23.
Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial-bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the main MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population. Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair.
骨组织在干细胞的支持下不断更新。最近的研究表明,血管周围间充质干细胞(MSCs)参与长骨的更新。颅面骨是扁平骨,其胚胎起源与长骨不同。颅面骨MSCs的身份和调控微环境仍然未知。在这里,我们确定缝合线间充质中的Gli1+细胞是颅面骨的主要MSC群体。它们与脉管系统无关,在成体中产生所有颅面骨,并在损伤修复过程中被激活。Gli1+细胞在体外是典型的MSCs。Gli1+细胞的消融导致颅缝早闭和颅骨生长停滞,表明这些细胞是不可或缺的干细胞群体。患有颅缝早闭的Twist1(+/-)小鼠在缝合线中的Gli1+ MSCs减少,这表明颅缝早闭可能是由于缝合线干细胞减少所致。我们的研究表明,颅面缝合线为维持颅面骨稳态和修复的MSCs提供了独特的微环境。