2. Academic Validation
  3. Identification and characterization of NFATc1+ skeletal stem cells in bone regeneration

Identification and characterization of NFATc1+ skeletal stem cells in bone regeneration

  • Cell Rep. 2022 Nov 8;41(6):111599. doi: 10.1016/j.celrep.2022.111599.
Fanyuan Yu 1,  Feifei Li 2,  Peng Yu 3,  Bin Zhou 4,  Ling Ye 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 2 State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 3 State Key Laboratory of Polymer Materials Engineering, College of Polymer Science and Engineering, Sichuan University, Chengdu, China.
  • 4 Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
  • 5 State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: yeling@scu.edu.cn.
PMID: 36351390 DOI: 10.1016/j.celrep.2022.111599
Abstract

Skeletal stem cells (SSCs) fuel adult bone with stemness resources to maintain homeostasis and support regeneration, which depends on the precise determination of the osteogenic lineage commitment of SSCs. In this study, using Cre-loxP reporter lineage tracking, we identified and characterized a population of NFATc1+ SSCs in bone regeneration. Pre-existing NFATc1+ SSCs are involved in early bone callus formation. Subsequently, these NFATc1+ SSCs produce osteolineage descendants in the subsequent stages of regeneration. The CA2+-triggered transcriptional activity of NFATc1 constitutes the pre-imprinted memory of the trajectory to intrinsically orchestrate osteogenesis of SSCs. Inhibition of CA2+/NFATc1 signaling in SSCs directly impairs osteogenesis and bone regeneration. In summary, our findings provide a mechanistic understanding of adult bone regeneration through the regulation of NFATc1+ SSCs.

Keywords

CP: Developmental biology; NFATc1; bone regeneration; lineage commitment; osteogenesis; skeletal stem cell.

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