Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing

Zhang, Hao; Wang, Renkai; Wang, Guangchao; Zhang, Bo; Wang, Chao; Li, Di; Ding, Chen; Wei, Qiang; Fan, Zhenyu; Tang, Hao; Ji, Fang

doi:10.3389/fendo.2021.666140

Cited by 29 publications

(23 citation statements)

References 35 publications

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“…Both matrixes were generated by the same platform annotation chip, so we considered that there were no data differences between groups. GSE142786 matrix contains single-cell gene expression profiles derived from 2 samples from patients 0 days post-fracture and 30 days post-fracture (31). Details about these databases and samples can be found in Table 1.…”

Section: Data Downloaded and Pre-processingmentioning

confidence: 99%

Identification of Up-Regulated ANXA3 Resulting in Fracture Non-Union in Patients With T2DM

Liu

et al. 2022

Front. Endocrinol.

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Diabetes mellitus is a metabolic disorder that increases fracture risk and interferes with bone formation and impairs fracture healing. Genomic studies on diabetes and fracture healing are lacking. We used a weighted co-expression network analysis (WGCNA) method to identify susceptibility modules and hub genes associated with T2DM and fracture healing. First, we downloaded the GSE95849, GSE93213, GSE93215, and GSE142786 data from the Gene Expression Omnibus (GEO) website, analyzed differential expression genes and constructed a WGCNA network. Second, we screened out 30 hub genes, which were found to be enriched in neutrophil activation, translational initiation, RAGE receptor binding, propanoate metabolism, and other pathways through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analyses. Third, we searched for genes related to bone metabolism and fracture healing in the published genome-wide single nucleotide polymorphism (SNP) data, built a protein-protein interaction (PPI) network with hub genes, and found that they were associated with metabolic process, blood vessel development, and extracellular matrix organization. ANXA3 was identified as the biomarker based on gene expression and correlation analysis. And the AUC value of it was 0.947. Fourth, we explored that ANXA3 was associated with neutrophils in fracture healing process by single-cell RNA sequencing analysis. Finally, we collected clinical patient samples and verified the expression of ANXA3 by qRT-PCR in patents with T2DM and fracture non-union. In conclusion, this is the first genomics study on the effect of T2DM on fracture healing. Our study identified some characteristic modules and hub genes in the etiology of T2DM-associated fracture non-union, which may help to further investigate the molecular mechanisms. Up-regulated ANXA3 potentially contributed to fracture non-union in T2DM by mediating neutrophils. It can be a prognostic biomarker and potential therapeutic target.

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Section: Data Downloaded and Pre-processingmentioning

confidence: 99%

Identification of Up-Regulated ANXA3 Resulting in Fracture Non-Union in Patients With T2DM

Liu

et al. 2022

Front. Endocrinol.

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“…Circulating immune cells also influence bone states ( 56 , 57 ). Aging and impaired circulating monocytes were chemotactic to bone lesions.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals in vivo osteoimmunology interactions between the immune and skeletal systems

et al. 2023

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BackgroundWhile osteoimmunology interactions between the immune and skeletal systems are known to play an important role in osteoblast development, differentiation and bone metabolism related disease like osteoporosis, such interactions in either bone microenvironment or peripheral circulation in vivo at the single-cell resolution have not yet been characterized.MethodsWe explored the osteoimmunology communications between immune cells and osteoblastic lineage cells (OBCs) by performing CellphoneDB and CellChat analyses with single-cell RNA sequencing (scRNA-seq) data from human femoral head. We also explored the osteoimmunology effects of immune cells in peripheral circulation on skeletal phenotypes. We used a scRNA-seq dataset of peripheral blood monocytes (PBMs) to perform deconvolution analysis. Then weighted gene co-expression network analysis (WGCNA) was used to identify monocyte subtype-specific subnetworks. We next used cell-specific network (CSN) and the least absolute shrinkage and selection operator (LASSO) to analyze the correlation of a gene subnetwork identified by WGCNA with bone mineral density (BMD).ResultsWe constructed immune cell and OBC communication networks and further identified L-R genes, such as JAG1 and NOTCH1/2, with ossification related functions. We also found a Mono4 related subnetwork that may relate to BMD variation in both older males and postmenopausal female subjects.ConclusionsThis is the first study to identify numerous ligand-receptor pairs that likely mediate signals between immune cells and osteoblastic lineage cells. This establishes a foundation to reveal advanced and in-depth osteoimmunology interactions to better understand the relationship between local bone microenvironment and immune cells in peripheral blood and the impact on bone phenotypes.

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“…In the meanwhile, a recent single-cell sequencing study revealed that skeletal muscle-derived mesenchymal progenitors also engage in bone repair, which will explain why adjacent tissues also matter ( Julien et al, 2021 ). In addition, Zhang H. et al (2021) suggest that B cells are key regulators of bone healing in the bone marrow microenvironment due to the opposite pattern between B cells and bone formation and resorption activities. Considering the fact that outcomes of bone defect healing are uncertain under the influence of different risk factors, such as age, nutritional status, and contamination degree ( Nicholson et al, 2021 ), we suspected that differences in the bone defect microenvironment may contribute to it.…”

Section: Bone Defect Microenvironment and Bone Healing Mechanismmentioning

confidence: 99%

Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

Zhang

Feng

et al. 2022

Front. Bioeng. Biotechnol.

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The treatment of bone defects is still an intractable clinical problem, despite the fact that numerous treatments are currently available. In recent decades, bone engineering scaffolds have become a promising tool to fill in the defect sites and remedy the deficiencies of bone grafts. By virtue of bone formation, vascular growth, and inflammation modulation, the combination of bone engineering scaffolds with cell-based and cell-free therapy is widely used in bone defect repair. As a key element of cell-free therapy, exosomes with bioactive molecules overcome the deficiencies of cell-based therapy and promote bone tissue regeneration via the potential of osteogenesis, angiogenesis, and inflammation modulation. Hence, this review aimed at overviewing the bone defect microenvironment and healing mechanism, summarizing current advances in bone engineering scaffolds and exosomes in bone defects to probe for future applications.

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Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing

Cited by 29 publications

References 35 publications

Identification of Up-Regulated ANXA3 Resulting in Fracture Non-Union in Patients With T2DM

Identification of Up-Regulated ANXA3 Resulting in Fracture Non-Union in Patients With T2DM

Single-cell RNA sequencing reveals in vivo osteoimmunology interactions between the immune and skeletal systems

Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

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