Identification of the Metaphyseal Skeletal Stem Cell Building Trabecular Bone

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Feb 23

PMID 38394209

Authors

Guan Yang

Qi He

Xiaoxiao Guo

Rong-Yu Li

Jingting Lin

Yiming Lang

Wanyu Tao

Wenjia Liu

Huisang Lin

Shilai Xing

Yini Qi

Zhongliang Xie

Jing-Dong J Han

Bin Zhou

Yan Teng

Xiao Yang

Affiliations

Soon will be listed here.

Abstract

Skeletal stem cells (SSCs) that are capable of self-renewal and multipotent differentiation contribute to bone development and homeostasis. Several populations of SSCs at different skeletal sites have been reported. Here, we identify a metaphyseal SSC (mpSSC) population whose transcriptional landscape is distinct from other bone mesenchymal stromal cells (BMSCs). These mpSSCs are marked by Sstr2 or PdgfrbKitl, located just underneath the growth plate, and exclusively derived from hypertrophic chondrocytes (HCs). These HC-derived mpSSCs have properties of self-renewal and multipotency in vitro and in vivo, producing most HC offspring postnatally. HC-specific deletion of Hgs, a component of the endosomal sorting complex required for transport, impairs the HC-to-mpSSC conversion and compromises trabecular bone formation. Thus, mpSSC is the major source of BMSCs and osteoblasts in bone marrow, supporting the postnatal trabecular bone formation.

Citing Articles

Unveiling two distinct osteolineage cell populations linked to age-related osteoporosis in adult mice through integrative single-cell analyses.

Zhou B, Huang H, Ding Z, Luo K, Chen Y, Han Y Cell Mol Life Sci. 2025; 82(1):106.

PMID: 40067455 PMC: 11896952. DOI: 10.1007/s00018-025-05597-w.

Skeletal stem and progenitor cells in bone physiology, ageing and disease.

Melis S, Trompet D, Chagin A, Maes C Nat Rev Endocrinol. 2024; 21(3):135-153.

PMID: 39379711 DOI: 10.1038/s41574-024-01039-y.

Hydrolyzed egg yolk peptide prevented osteoporosis by regulating Wnt/β-catenin signaling pathway in ovariectomized rats.

Chen C, Huang L, Chen Y, Jin J, Xu Z, Liu F Sci Rep. 2024; 14(1):10227.

PMID: 38702443 PMC: 11068896. DOI: 10.1038/s41598-024-60514-8.

References

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z . clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Camb). 2021; 2(3):100141. PMC: 8454663. DOI: 10.1016/j.xinn.2021.100141. View

Zhou X, von der Mark K, Henry S, Norton W, Adams H, de Crombrugghe B . Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet. 2014; 10(12):e1004820. PMC: 4256265. DOI: 10.1371/journal.pgen.1004820. View

Ambrosi T, Longaker M, Chan C . A Revised Perspective of Skeletal Stem Cell Biology. Front Cell Dev Biol. 2019; 7:189. PMC: 6753172. DOI: 10.3389/fcell.2019.00189. View

Zhu M, Chen M, Lichtler A, OKeefe R, Chen D . Tamoxifen-inducible Cre-recombination in articular chondrocytes of adult Col2a1-CreER(T2) transgenic mice. Osteoarthritis Cartilage. 2007; 16(1):129-30. PMC: 2271067. DOI: 10.1016/j.joca.2007.08.001. View

Menon S, Salhotra A, Shailendra S, Tevlin R, Ransom R, Januszyk M . Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis. Nat Commun. 2021; 12(1):4640. PMC: 8324898. DOI: 10.1038/s41467-021-24801-6. View

Henry S, Jang C, Deng J, Zhang Z, Behringer R, de Crombrugghe B . Generation of aggrecan-CreERT2 knockin mice for inducible Cre activity in adult cartilage. Genesis. 2009; 47(12):805-14. PMC: 3951921. DOI: 10.1002/dvg.20564. View

Murphy M, Koepke L, Lopez M, Tong X, Ambrosi T, Gulati G . Articular cartilage regeneration by activated skeletal stem cells. Nat Med. 2020; 26(10):1583-1592. PMC: 7704061. DOI: 10.1038/s41591-020-1013-2. View

Mizuhashi K, Ono W, Matsushita Y, Sakagami N, Takahashi A, Saunders T . Resting zone of the growth plate houses a unique class of skeletal stem cells. Nature. 2018; 563(7730):254-258. PMC: 6251707. DOI: 10.1038/s41586-018-0662-5. View

Matsushita Y, Chu A, Tsutsumi-Arai C, Orikasa S, Nagata M, Wong S . The fate of early perichondrial cells in developing bones. Nat Commun. 2022; 13(1):7319. PMC: 9705540. DOI: 10.1038/s41467-022-34804-6. View

10.

Ding L, Saunders T, Enikolopov G, Morrison S . Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012; 481(7382):457-62. PMC: 3270376. DOI: 10.1038/nature10783. View

11.

Storer M, Mahmud N, Karamboulas K, Borrett M, Yuzwa S, Gont A . Acquisition of a Unique Mesenchymal Precursor-like Blastema State Underlies Successful Adult Mammalian Digit Tip Regeneration. Dev Cell. 2020; 52(4):509-524.e9. DOI: 10.1016/j.devcel.2019.12.004. View

12.

Ye Q, Zhou J, He Q, Li R, Yang G, Zhang Y . SARS-CoV-2 infection in the mouse olfactory system. Cell Discov. 2021; 7(1):49. PMC: 8260584. DOI: 10.1038/s41421-021-00290-1. View

13.

Street K, Risso D, Fletcher R, Das D, Ngai J, Yosef N . Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics. 2018; 19(1):477. PMC: 6007078. DOI: 10.1186/s12864-018-4772-0. View

14.

Muruganandan S, Pierce R, Teguh D, Perez R, Bell N, Nguyen B . A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury. Nat Commun. 2022; 13(1):2515. PMC: 9076650. DOI: 10.1038/s41467-022-30247-1. 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.

Knopf F, Hammond C, Chekuru A, Kurth T, Hans S, Weber C . Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin. Dev Cell. 2011; 20(5):713-24. DOI: 10.1016/j.devcel.2011.04.014. View

17.

Morikawa S, Mabuchi Y, Kubota Y, Nagai Y, Niibe K, Hiratsu E . Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med. 2009; 206(11):2483-96. PMC: 2768869. DOI: 10.1084/jem.20091046. View

18.

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

19.

Park J, Gebhardt M, Golovchenko S, Perez-Branguli F, Hattori T, Hartmann C . Dual pathways to endochondral osteoblasts: a novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage. Biol Open. 2015; 4(5):608-21. PMC: 4434812. DOI: 10.1242/bio.201411031. View

20.

Madisen L, Zwingman T, Sunkin S, Oh S, Zariwala H, Gu H . A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci. 2009; 13(1):133-40. PMC: 2840225. DOI: 10.1038/nn.2467. View