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Nature. 2018 Oct;562(7725):133-139. doi: 10.1038/s41586-018-0554-8. Epub 2018 Sep 24.

Discovery of a periosteal stem cell mediating intramembranous bone formation.

Author information

1
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
2
Flow Cytometry Core Facility, Weill Cornell Medicine, New York, NY, USA.
3
Genomics Resources Core Facility, Weill Cornell Medicine, New York, NY, USA.
4
Pathology and Laboratory Medicine Core Facility, Weill Cornell Medicine, New York, NY, USA.
5
Department of Medicine, University of Massachusetts Medical School, North Worcester, MA, USA.
6
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
7
Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
8
Research Division, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA.
9
Division of Adult Reconstruction and Joint Replacement, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA.
10
Cancer Genomics and Evolutionary Dynamics, Weill Cornell Medicine, New York, NY, USA.
11
New York Genome Center, New York, NY, USA.
12
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. mag3003@med.cornell.edu.

Abstract

Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of cells owing to physical separation by the bone cortex. The skeletal stem cell that gives rise to endosteal osteoblasts has been extensively studied; however, the identity of periosteal stem cells remains unclear1-5. Here we identify a periosteal stem cell (PSC) that is present in the long bones and calvarium of mice, displays clonal multipotency and self-renewal, and sits at the apex of a differentiation hierarchy. Single-cell and bulk transcriptional profiling show that PSCs display transcriptional signatures that are distinct from those of other skeletal stem cells and mature mesenchymal cells. Whereas other skeletal stem cells form bone via an initial cartilage template using the endochondral pathway4, PSCs form bone via a direct intramembranous route, providing a cellular basis for the divergence between intramembranous versus endochondral developmental pathways. However, there is plasticity in this division, as PSCs acquire endochondral bone formation capacity in response to injury. Genetic blockade of the ability of PSCs to give rise to bone-forming osteoblasts results in selective impairments in cortical bone architecture and defects in fracture healing. A cell analogous to mouse PSCs is present in the human periosteum, raising the possibility that PSCs are attractive targets for drug and cellular therapy for skeletal disorders. The identification of PSCs provides evidence that bone contains multiple pools of stem cells, each with distinct physiologic functions.

PMID:
30250253
PMCID:
PMC6193396
[Available on 2019-03-24]
DOI:
10.1038/s41586-018-0554-8

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