Back to Search
Start Over
Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis
- Source :
- Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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.<br />Cranial sutures are major growth centers for the skull vault and premature fusion leads to pathological fusion, craniosynostosis. Here the authors isolate Wnt responsive skeletal stem and progenitor cells from sutures, that can be transplanted together with Wnt3a protein to repair craniosynostosis in a mouse model.
- Subjects :
- 0301 basic medicine
Pathology
General Physics and Astronomy
Pathogenesis
0302 clinical medicine
Cranial vault
Musculoskeletal System
Wnt Signaling Pathway
Cells, Cultured
Mice, Knockout
Fibrous joint
education.field_of_study
Multidisciplinary
Coronal craniosynostosis
Stem Cells
Bone development
Cell Differentiation
Experimental models of disease
medicine.anatomical_structure
Stem cell
medicine.medical_specialty
Science
Population
Mice, Transgenic
Article
General Biochemistry, Genetics and Molecular Biology
Craniosynostosis
Craniosynostoses
03 medical and health sciences
Axin Protein
Wnt3A Protein
medicine
Animals
Progenitor cell
education
Cell Proliferation
business.industry
Gene Expression Profiling
Twist-Related Protein 1
Mesenchymal stem cell
Cranial Sutures
General Chemistry
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Mesenchymal stem cells
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....0d70d55bf7e683c0a0cb93ffdee089d8