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Related Experiment Video

Updated: Jan 8, 2026

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations
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Deciphering B Cell Heterogeneity and Pathogenic Mechanisms in Osteoporosis Through Single-Cell RNA Sequencing.

Taolve Zhou1, Jiayuan Zheng1, Yujun Sun1

  • 1Department of Trauma Orthopedics, Foot & Ankle Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China, sysu.edu.cn.

Biomed Research International
|December 17, 2025
PubMed
Summary

B cells, particularly precursor B cells, are implicated in osteoporosis progression through inflammation and unfolded protein responses. Two key signaling pathways, MIF-(CD74+CXCR4) and LGALS9-CD45, were identified as potential therapeutic targets for osteoporosis treatment.

Keywords:
B cell heterogeneityB cell subpopulationsLGALS9-CD45 signalingMIF-(CD74+CXCR4) signalingimmune microenvironmentosteoporosisscRNA-seqsingle-cell RNA sequencing

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Area of Science:

  • Immunology
  • Bone Biology
  • Genomics

Background:

  • Osteoporosis is a skeletal disorder marked by low bone density and microarchitectural deterioration, increasing fracture risk.
  • Understanding the immune system's role, specifically B cell subpopulations, is crucial for elucidating osteoporosis pathogenesis.

Purpose of the Study:

  • To investigate the specific roles and functions of distinct B cell subpopulations in osteoporosis.
  • To identify key molecular pathways driving B cell involvement in osteoporosis using single-cell RNA sequencing.

Main Methods:

  • Single-cell RNA sequencing data from human femoral head tissue of osteoporosis patients and controls were analyzed.
  • Bioinformatic analyses included data preprocessing, clustering, cell type annotation, enrichment, trajectory, and intercellular communication analysis.

Main Results:

  • Six B cell subpopulations were identified, with a higher proportion of precursor B cells in osteoporosis patients.
  • B cells contribute to osteoporosis via inflammatory activation and unfolded protein response, with enhanced intercellular signaling observed in patients.
  • The MIF-(CD74+CXCR4) and LGALS9-CD45 signaling pathways were identified as critical regulators in osteoporosis progression.

Conclusions:

  • B cell heterogeneity and function are significant in osteoporosis pathogenesis.
  • Identified signaling pathways offer potential novel therapeutic targets for osteoporosis treatment.