International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution

  • Ying Liu (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Yan Chen (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Xiao-Hua Li (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Chong Cao (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Hui-Xi Zhang (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Cui Zhou (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Yu Chen (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Yun Gong (Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine) ;
  • Jun-Xiao Yang (Department of Orthopedics, Xiangya Hospital, Central South University) ;
  • Liang Cheng (Department of Orthopedics and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University) ;
  • Xiang-Ding Chen (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Hui Shen (Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine) ;
  • Hong-Mei Xiao (School of Basic Medical Science, Central South University) ;
  • Li-Jun Tan (Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University) ;
  • Hong-Wen Deng (Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine)
  • Received : 2022.06.22
  • Accepted : 2022.11.21
  • Published : 2023.08.30
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Abstract

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions: Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

Keywords

Acknowledgement

This research was benefited by grants from the National Institutes of Health (R01AR069055, U19AG055373, P20GM109036, R01AG061917), National Natural Science Foundation of China (NSFC) (Grant No. 81902277 and 81570807), National Key R&D Program of China (Grant No. 2017YFC1001100), Natural Science Foundation of Hunan Province (S2019JJQNJJ2093), Changsha Science and technology project (kq1907153), Central South University (Grant Nos. 164990007, 2018zzts886), and Xiangya Clinical Big Data Project (xyyydsj9).

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