Discovery of a periosteal stem cell mediating intramembranous bone formation

Shawon Debnath, Alisha R. Yallowitz, Jason McCormick, Sarfaraz Lalani, Tuo Zhang, Ren Xu, Na Li, Yifang Liu, Yeon Suk Yang, Mark Eiseman, Jae-Hyuck Shim, Meera Hameed, John H. Healey, Mathias P. Bostrom, Dan Avi Landau and Matthew B. Greenblatt ()
Additional contact information
Shawon Debnath: Weill Cornell Medicine
Alisha R. Yallowitz: Weill Cornell Medicine
Jason McCormick: Weill Cornell Medicine
Sarfaraz Lalani: Weill Cornell Medicine
Tuo Zhang: Weill Cornell Medicine
Ren Xu: Weill Cornell Medicine
Na Li: Weill Cornell Medicine
Yifang Liu: Weill Cornell Medicine
Yeon Suk Yang: University of Massachusetts Medical School
Mark Eiseman: Weill Cornell Medicine
Jae-Hyuck Shim: University of Massachusetts Medical School
Meera Hameed: Memorial Sloan Kettering Cancer Center
John H. Healey: Memorial Sloan Kettering Cancer Center
Mathias P. Bostrom: Hospital for Special Surgery
Dan Avi Landau: Weill Cornell Medicine
Matthew B. Greenblatt: Weill Cornell Medicine

Nature, 2018, vol. 562, issue 7725, 133-139

Abstract: 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.

Keywords: Periosteal Stem Cells (PSCs); Intramembranous Bone Formation; Multipotent Clones; Bone-forming Capacity; Human Periosteum (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (11)

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DOI: 10.1038/s41586-018-0554-8

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