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Identification of Postn+ periosteal progenitor cells with bone regenerative potential
Bei Yin, Fangyuan Shen, Qingge Ma, Yongcheng Liu, Xianglong Han, Xuyu Cai, Yu Shi, Ling Ye
Bei Yin, Fangyuan Shen, Qingge Ma, Yongcheng Liu, Xianglong Han, Xuyu Cai, Yu Shi, Ling Ye
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Research Article Bone biology

Identification of Postn+ periosteal progenitor cells with bone regenerative potential

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Abstract

Bone contains multiple pools of skeletal stem/progenitor cells (SSPCs), and SSPCs in periosteal compartments are known to exhibit higher regenerative potential than those in BM and endosteal compartments. However, the in vivo identity and hierarchical relationships of periosteal SSPCs (P-SSPCs) remain unclear due to a lack of reliable markers to distinguish BM SSPCs and P-SSPCs. Here, we found that periosteal mesenchymal progenitor cells (P-MPs) in periosteum can be identified based on Postn-CreERT2 expression. Postn-expressing periosteal subpopulation produces osteolineage descendants that fuel bones to maintain homeostasis and support regeneration. Notably, Postn+ P-MPs are likely derived from Gli1+ skeletal stem cells (SSCs). Ablation of Postn+ cells results in impairments in homeostatic cortical bone architecture and defects in fracture repair. Genetic deletion of Igf1r in Postn+ cells dampens bone fracture healing. In summary, our study provides a mechanistic understanding of bone regeneration through the regulation of region-specific Postn+ P-MPs.

Authors

Bei Yin, Fangyuan Shen, Qingge Ma, Yongcheng Liu, Xianglong Han, Xuyu Cai, Yu Shi, Ling Ye

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Figure 1

Identification of Postn+ P-MPs utilizing scRNA transcriptome profiling.

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Identification of Postn+ P-MPs utilizing scRNA transcriptome profiling.
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(A) UMAP revealed cellular heterogeneity of mesenchymal cells in bone callus with 7 distinct clusters by integrating day 7, day 10, and day 14 data set. (B) Pseudotime ordering of callus mesenchymal cells by pseudotime Monocle trajectory plot. (C) Postn expression in each cell along the pseudotime axis. (D) The cellular interaction among distinct clusters based on CellChat analysis. (E) Representative growth factors and cytokines in each cluster. See also Supplemental Figure 1.

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