Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis

Siddharth Menon, Ankit Salhotra, Siny Shailendra, Ruth Tevlin, Ryan C. Ransom, Michael Januszyk, Charles K. F. Chan, Björn Behr, Derrick C. Wan, Michael T. Longaker () and Natalina Quarto ()
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Siddharth Menon: Stanford University School of Medicine
Ankit Salhotra: Stanford University School of Medicine
Siny Shailendra: Stanford University School of Medicine
Ruth Tevlin: Stanford University School of Medicine
Ryan C. Ransom: Stanford University School of Medicine
Michael Januszyk: Stanford University School of Medicine
Charles K. F. Chan: Stanford University School of Medicine
Björn Behr: University Hospital Bergmannsheil Bochum
Derrick C. Wan: Stanford University School of Medicine
Michael T. Longaker: Stanford University School of Medicine
Natalina Quarto: Stanford University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Cranial sutures are major growth centers for the calvarial vault, and their premature fusion leads to a pathologic condition called craniosynostosis. This study investigates whether skeletal stem/progenitor cells are resident in the cranial sutures. Prospective isolation by FACS identifies this population with a significant difference in spatio-temporal representation between fusing versus patent sutures. Transcriptomic analysis highlights a distinct signature in cells derived from the physiological closing PF suture, and scRNA sequencing identifies transcriptional heterogeneity among sutures. Wnt-signaling activation increases skeletal stem/progenitor cells in sutures, whereas its inhibition decreases. Crossing Axin2LacZ/+ mouse, endowing enhanced Wnt activation, to a Twist1+/− mouse model of coronal craniosynostosis enriches skeletal stem/progenitor cells in sutures restoring patency. Co-transplantation of these cells with Wnt3a prevents resynostosis following suturectomy in Twist1+/− mice. Our study reveals that decrease and/or imbalance of skeletal stem/progenitor cells representation within sutures may underlie craniosynostosis. These findings have translational implications toward therapeutic approaches for craniosynostosis.

Date: 2021
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DOI: 10.1038/s41467-021-24801-6

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