Research ArticleBone

BMPR1A maintains skeletal stem cell properties in craniofacial development and craniosynostosis

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Science Translational Medicine  03 Mar 2021:
Vol. 13, Issue 583, eabb4416
DOI: 10.1126/scitranslmed.abb4416

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Signaling and suture stem cells

Suture stem cells give rise to craniofacial bone, and premature suture closure (craniosynostosis) is a common congenital deformity. Here, Maruyama et al. studied the role of bone morphogenetic protein (BMP) signaling in suture stem cell dysregulation and craniosynostosis. They found that deletion of BMP type I receptor, Bmpr1a, in suture stem cells caused craniofacial abnormalities in mice, including abnormal ossification and suture closure at 2 months of age. Loss of BMPR1A was associated with enhanced proliferation but loss of self-renewal in suture stem cells. Cells from patients were also assessed. Results demonstrate how BMPR1A regulates stemness, clonal expansion, and osteogenesis of suture stem cells, contributing to craniofacial bone development.


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 Bmpr1a 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.

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