Abstract

Osteoblasts continuously replenished by osteoblast progenitor cells form the basis of bone development, maintenance, and regeneration. Mesenchymal stem cells (MSCs) from various tissues can differentiate into the progenitor cell of osteogenic lineage and serve as the main source of osteoblasts. They also respond flexibly to regenerative and anabolic signals emitted by the surrounding microenvironment, thereby maintaining bone homeostasis and participating in bone remodeling. However, MSCs exhibit heterogeneity at multiple levels including different tissue sources and subpopulations which exhibit diversified gene expression and differentiation capacity, and surface markers used to predict cell differentiation potential remain to be further elucidated. The rapid advancement of lineage tracing methods and single-cell technology has made substantial progress in the characterization of osteogenic stem/progenitor cell populations in MSCs. Here, we reviewed the research progress of scRNA-seq technology in the identification of osteogenic markers and differentiation pathways, MSC-related new insights drawn from single-cell technology combined with experimental technology, and recent findings regarding the interaction between stem cell fate and niche in homeostasis and pathological process.

Highlights

  • The bone formation depends on the activation and recruitment of osteogenic stem/progenitor cells during bone development, reconstruction, and fracture repair

  • With the emergence of numerous Mesenchymal stem cells (MSCs)-related studies, researchers have meticulously named the subgroups of MSCs such as embryonic Skeletal Stem/progenitor Cell, Bone Marrow Mesenchymal Cell (BMSC), Periosteal Stem Cell (PSC), etc., based on tissue origin, the developmental stage of donors, and differentiation characteristics

  • We summarized the heterogeneity of MSCs derived from limb buds and postnatal distinct hard tissues as determined by single-cell resolution studies and the biologic functions and characteristics of new labeled stem/progenitor subpopulations

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Summary

INTRODUCTION

The bone formation depends on the activation and recruitment of osteogenic stem/progenitor cells during bone development, reconstruction, and fracture repair. MSCs have long been regarded as a direct source of osteogenic lineage progenitor cells in bone tissue. Their source is complex and correlates with stage and tissue specificity. With the emergence of numerous MSC-related studies, researchers have meticulously named the subgroups of MSCs such as embryonic Skeletal Stem/progenitor Cell (eSSPC), Bone Marrow Mesenchymal Cell (BMSC), Periosteal Stem Cell (PSC), etc., based on tissue origin, the developmental stage of donors, and differentiation characteristics. We summarized the heterogeneity of MSCs derived from limb buds and postnatal distinct hard tissues as determined by single-cell resolution studies and the biologic functions and characteristics of new labeled stem/progenitor subpopulations. We focused on the research progress on the osteogenic subpopulation of cre-targeted MSCs and the interaction between the osteogenic niche and precursor cells

TRADITIONAL MSCS IDENTIFICATION METHODS
Identification of MSCs in Embryonic and Fetal Limb Buds
Hard Tissue-Derived MSCs in Postnatal Stages
SCRNA-SEQ ON CRE-TARGETED MSCS IN TRANSGENIC MICE
SINGLE-CELL ANALYSIS OF MSC IN RESPONSE TO MICROENVIRONMENT
Tooth Niche Cell Regulates MSCs Homeostasis
The Lineage Transition of MSCs in Senescent
MSCs Under the Crosstalk With Tumor Microenvironment
Injury-Induced Niche Regulates MSC Behavior
CONCLUSION AND FUTURE PERSPECTIVES
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