Center for Oral Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Department of Dentistry, University of Rochester Medical Center, Rochester, NY 14642, USA.
Sci Transl Med. 2021 Mar 3;13(583). doi: 10.1126/scitranslmed.abb4416.
Skeletal stem cells from the suture mesenchyme, which are referred to as suture stem cells (SuSCs), exhibit long-term self-renewal, clonal expansion, and multipotency. These SuSCs reside in the suture midline and serve as the skeletal stem cell population responsible for calvarial development, homeostasis, injury repair, and regeneration. The ability of SuSCs to engraft in injury site to replace the damaged skeleton supports their potential use for stem cell-based therapy. Here, we identified BMPR1A as essential for SuSC self-renewal and SuSC-mediated bone formation. SuSC-specific disruption of in mice caused precocious differentiation, leading to craniosynostosis initiated at the suture midline, which is the stem cell niche. We found that BMPR1A is a cell surface marker of human SuSCs. Using an ex vivo system, we showed that SuSCs maintained stemness properties for an extended period without losing the osteogenic ability. This study advances our knowledge base of congenital deformity and regenerative medicine mediated by skeletal stem cells.
骨缝间质中的骨骼干/祖细胞（suture stem cells，SuSCs），被称为缝间干/祖细胞，具有长期自我更新、克隆扩增和多能性。这些 SuSCs 位于骨缝中线，是负责颅骨发育、稳态、损伤修复和再生的骨骼干/祖细胞群体。SuSCs 能够在损伤部位植入以替代受损骨骼的能力支持了它们在基于干细胞的治疗中的潜在用途。在这里，我们确定 BMPR1A 对 SuSC 自我更新和 SuSC 介导的骨形成至关重要。在小鼠中特异性敲除 SuSC 中的 导致过早分化，导致颅缝融合提前发生在骨缝中线，这是干细胞龛所在的位置。我们发现 BMPR1A 是人类 SuSCs 的细胞表面标志物。使用体外系统，我们表明 SuSCs 可以在不丧失成骨能力的情况下延长维持干细胞特性的时间。这项研究推进了我们对由骨骼干/祖细胞介导的先天性畸形和再生医学的认识基础。
