Skeletal Stem Cells in Bone Development, Homeostasis, and Disease

Overview

Journal Protein Cell

Publisher Oxford University Press

Specialties Biochemistry
Cell Biology

Date 2024 Mar 5

PMID 38442300

Authors

Guixin Yuan

Xixi Lin

Ying Liu

Matthew B Greenblatt

Ren Xu

Affiliations

Soon will be listed here.

Abstract

Tissue-resident stem cells are essential for development and repair, and in the skeleton, this function is fulfilled by recently identified skeletal stem cells (SSCs). However, recent work has identified that SSCs are not monolithic, with long bones, craniofacial sites, and the spine being formed by distinct stem cells. Recent studies have utilized techniques such as fluorescence-activated cell sorting, lineage tracing, and single-cell sequencing to investigate the involvement of SSCs in bone development, homeostasis, and disease. These investigations have allowed researchers to map the lineage commitment trajectory of SSCs in different parts of the body and at different time points. Furthermore, recent studies have shed light on the characteristics of SSCs in both physiological and pathological conditions. This review focuses on discussing the spatiotemporal distribution of SSCs and enhancing our understanding of the diversity and plasticity of SSCs by summarizing recent discoveries.

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References

Zhou B, Yue R, Murphy M, Peyer J, Morrison S . Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell. 2014; 15(2):154-68. PMC: 4127103. DOI: 10.1016/j.stem.2014.06.008. View

Chan C, Gulati G, Sinha R, Tompkins J, Lopez M, Carter A . Identification of the Human Skeletal Stem Cell. Cell. 2018; 175(1):43-56.e21. PMC: 6400492. DOI: 10.1016/j.cell.2018.07.029. View

Jacome-Galarza C, Percin G, Muller J, Mass E, Lazarov T, Eitler J . Developmental origin, functional maintenance and genetic rescue of osteoclasts. Nature. 2019; 568(7753):541-545. PMC: 6910203. DOI: 10.1038/s41586-019-1105-7. View

Mendez-Ferrer S, Michurina T, Ferraro F, Mazloom A, MacArthur B, Lira S . Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010; 466(7308):829-34. PMC: 3146551. DOI: 10.1038/nature09262. View

Wilk K, Yeh S, Mortensen L, Ghaffarigarakani S, Lombardo C, Bassir S . Postnatal Calvarial Skeletal Stem Cells Expressing PRX1 Reside Exclusively in the Calvarial Sutures and Are Required for Bone Regeneration. Stem Cell Reports. 2017; 8(4):933-946. PMC: 5390237. DOI: 10.1016/j.stemcr.2017.03.002. View

Zeller R, Lopez-Rios J, Zuniga A . Vertebrate limb bud development: moving towards integrative analysis of organogenesis. Nat Rev Genet. 2009; 10(12):845-58. DOI: 10.1038/nrg2681. View

McLellan M, Rosenthal N, Pinto A . Cre-loxP-Mediated Recombination: General Principles and Experimental Considerations. Curr Protoc Mouse Biol. 2017; 7(1):1-12. DOI: 10.1002/cpmo.22. View

Ma L, Chang Q, Pei F, Liu M, Zhang W, Hong Y . Skull progenitor cell-driven meningeal lymphatic restoration improves neurocognitive functions in craniosynostosis. Cell Stem Cell. 2023; 30(11):1472-1485.e7. PMC: 10842404. DOI: 10.1016/j.stem.2023.09.012. View

Ambrosi T, Sinha R, Steininger H, Hoover M, Murphy M, Koepke L . Distinct skeletal stem cell types orchestrate long bone skeletogenesis. Elife. 2021; 10. PMC: 8289409. DOI: 10.7554/eLife.66063. View

10.

Kara N, Xue Y, Zhao Z, Murphy M, Comazzetto S, Lesser A . Endothelial and Leptin Receptor cells promote the maintenance of stem cells and hematopoiesis in early postnatal murine bone marrow. Dev Cell. 2023; 58(5):348-360.e6. PMC: 10035381. DOI: 10.1016/j.devcel.2023.02.003. View

11.

Clarke B . Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008; 3 Suppl 3:S131-9. PMC: 3152283. DOI: 10.2215/CJN.04151206. View

12.

Ambrosi T, Marecic O, McArdle A, Sinha R, Gulati G, Tong X . Aged skeletal stem cells generate an inflammatory degenerative niche. Nature. 2021; 597(7875):256-262. PMC: 8721524. DOI: 10.1038/s41586-021-03795-7. View

13.

Jin A, Xu H, Gao X, Sun S, Yang Y, Huang X . ScRNA-Seq Reveals a Distinct Osteogenic Progenitor of Alveolar Bone. J Dent Res. 2023; 102(6):645-655. DOI: 10.1177/00220345231159821. View

14.

Bianco P . "Mesenchymal" stem cells. Annu Rev Cell Dev Biol. 2014; 30:677-704. DOI: 10.1146/annurev-cellbio-100913-013132. View

15.

Worthley D, Churchill M, Compton J, Tailor Y, Rao M, Si Y . Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell. 2015; 160(1-2):269-84. PMC: 4436082. DOI: 10.1016/j.cell.2014.11.042. View

16.

Wang K, Xu C, Xie X, Jing Y, Chen P, Yadav S . Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force. J Dent Res. 2022; 101(6):695-703. PMC: 9124907. DOI: 10.1177/00220345211062585. View

17.

Matthews B, Novak S, Sbrana F, Funnell J, Cao Y, Buckels E . Heterogeneity of murine periosteum progenitors involved in fracture healing. Elife. 2021; 10. PMC: 7906599. DOI: 10.7554/eLife.58534. View

18.

Khosla S, Farr J, Tchkonia T, Kirkland J . The role of cellular senescence in ageing and endocrine disease. Nat Rev Endocrinol. 2020; 16(5):263-275. PMC: 7227781. DOI: 10.1038/s41574-020-0335-y. View

19.

Gulati G, Murphy M, Marecic O, Lopez M, Brewer R, Koepke L . Isolation and functional assessment of mouse skeletal stem cell lineage. Nat Protoc. 2018; 13(6):1294-1309. PMC: 6530903. DOI: 10.1038/nprot.2018.041. View

20.

Ono N, Ono W, Nagasawa T, Kronenberg H . A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones. Nat Cell Biol. 2014; 16(12):1157-67. PMC: 4250334. DOI: 10.1038/ncb3067. View