Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution

Ying Liu; Yan Chen; Xiao-Hua Li; Chong Cao; Hui-Xi Zhang; Cui Zhou; Yu Chen; Yun Gong; Jun-Xiao Yang; Liang Cheng; Xiang-Ding Chen; Hui Shen; Hong-Mei Xiao; Li-Jun Tan; Hong-Wen Deng

doi:10.15283/ijsc22101

Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution

Int J Stem Cells. 2023 Aug 30;16(3):342-355. doi: 10.15283/ijsc22101. Epub 2023 Apr 30.

Authors

Ying Liu¹, Yan Chen¹, Xiao-Hua Li¹, Chong Cao¹, Hui-Xi Zhang¹, Cui Zhou¹, Yu Chen¹, Yun Gong², Jun-Xiao Yang³, Liang Cheng⁴, Xiang-Ding Chen¹, Hui Shen², Hong-Mei Xiao^{5

6}, Li-Jun Tan¹, Hong-Wen Deng²

Affiliations

¹ Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China.
² Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
³ Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Orthopedics and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁵ School of Basic Medical Science, Central South University, Changsha, China.
⁶ Center of Reproductive Health, System Biology and Data Information, Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.

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: Bone marrow mesenchymal stem cells (BMMSCs); Cellular heterogeneity; Osteoblasts; Single-cell RNA sequencing (scRNA-seq).

Abstract

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