Ribosome biogenesis controls cranial suture MSC fate via the complement pathway in mouse and human iPSC models
Issued Date
2023-12-12
Resource Type
ISSN
22136711
Scopus ID
2-s2.0-85179471150
Pubmed ID
37977145
Journal Title
Stem Cell Reports
Volume
18
Issue
12
Start Page
2370
End Page
2385
Rights Holder(s)
SCOPUS
Bibliographic Citation
Stem Cell Reports Vol.18 No.12 (2023) , 2370-2385
Suggested Citation
Jariyasakulroj S., Zhang W., Bai J., Zhang M., Lu Z., Chen J.F. Ribosome biogenesis controls cranial suture MSC fate via the complement pathway in mouse and human iPSC models. Stem Cell Reports Vol.18 No.12 (2023) , 2370-2385. 2385. doi:10.1016/j.stemcr.2023.10.015 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/91554
Title
Ribosome biogenesis controls cranial suture MSC fate via the complement pathway in mouse and human iPSC models
Other Contributor(s)
Abstract
Disruption of global ribosome biogenesis selectively affects craniofacial tissues with unclear mechanisms. Craniosynostosis is a congenital craniofacial disorder characterized by premature fusion of cranial suture(s) with loss of suture mesenchymal stem cells (MSCs). Here we focused on ribosomopathy disease gene Snord118, which encodes a small nucleolar RNA (snoRNA), to genetically disturb ribosome biogenesis in suture MSCs using mouse and human induced pluripotent stem cell (iPSC) models. Snord118 depletion exhibited p53 activation, increased cell death, reduced proliferation, and premature osteogenic differentiation of MSCs, leading to suture growth and craniosynostosis defects. Mechanistically, Snord118 deficiency causes translational dysregulation of ribosomal proteins and downregulation of complement pathway genes. Further complement pathway disruption by knockout of complement C3a receptor 1 (C3ar1) exacerbated MSC and suture defects in mutant mice, whereas activating the complement pathway rescued MSC cell fate and suture growth defects. Thus, ribosome biogenesis controls MSC fate via the complement pathway to prevent craniosynostosis.