Ribosome biogenesis controls cranial suture MSC fate via the complement pathway in mouse and human iPSC models.
Snord118
complement pathway
craniosynostosis
human iPSC
ribosome biogenesis
suture mesenchymal stem cells
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
12 Dec 2023
12 Dec 2023
Historique:
received:
10
04
2023
revised:
22
10
2023
accepted:
23
10
2023
pubmed:
18
11
2023
medline:
18
11
2023
entrez:
17
11
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37977145
pii: S2213-6711(23)00417-4
doi: 10.1016/j.stemcr.2023.10.015
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2370-2385Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE030901
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG070681
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG075665
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.