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

Wang, Shengran and Greenbaum, Jonathan and Qiu, Chuan and Gong, Yun and Wang, Zun and Lin, Xu and Liu, Yong and He, Pei and Meng, Xianghe and Zhang, Qiang and Shen, Hui and Vemulapalli, Krishna Chandra and Sanchez, Fernando L. and Schiller, Martin R. and Xiao, Hongmei and Deng, Hongwen (2023) Single-cell RNA sequencing reveals in vivo osteoimmunology interactions between the immune and skeletal systems. Frontiers in Endocrinology, 14. ISSN 1664-2392

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Abstract

Background: While 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.

Methods: We 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).

Results: We 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.

Conclusions: This 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.

Item Type: Article
Subjects: STM Academic > Mathematical Science
Depositing User: Unnamed user with email support@stmacademic.com
Date Deposited: 09 Jul 2023 04:39
Last Modified: 14 Oct 2023 05:38
URI: http://article.researchpromo.com/id/eprint/1240

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