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基于基因芯片和单细胞 RNA 测序数据鉴定与骨质疏松症发病机制相关的 12 个枢纽基因。

Identification of 12 hub genes associated to the pathogenesis of osteoporosis based on microarray and single-cell RNA sequencing data.

机构信息

Department of Orthopedics Surgery, West China Hospital, Sichuan University, Orthopedic Research Institute, West China Hospital, Sichuan University, No. 37 Guo Xue Lane, Chengdu, 610041, Sichuan, China.

Department of Spine Surgery, Jiujiang No. 1 People's Hospital, Jiujiang, China.

出版信息

Funct Integr Genomics. 2023 May 27;23(2):186. doi: 10.1007/s10142-023-01116-x.

DOI:10.1007/s10142-023-01116-x
PMID:37243790
Abstract

Osteoporosis is a common disease, especially among the elderly. This study aimed to comprehensively examine the roles of immune microenvironment in osteoporosis pathogenesis. Expression profiles of GSE35959, GSE7158, and GSE13850 datasets were used to analyze differential expression and identify hub genes related to immune features. Based on the single-cell RNA sequencing (scRNA-seq) data of an osteoporosis patient, different cell types were classified and the relation between immune environment and osteoporosis was explored. Twelve hub genes significantly associated with immune features were selected and 11 subgroups were defined using scRNA-seq data. The expression of two hub genes (CDKN1A and TEFM) was greatly altered during the transformation from mesenchymal stem cells (MSCs) to osteoblasts. Chemokines and chemokine receptors were differentially enriched in different cell types. CXCL12 was high-expressed in MSCs. This study emphasized that immune microenvironment played a critical role in the pathogenesis of osteoporosis. Chemokines and chemokine receptors can modify cell development and affect the interactions among different cell types, leading to unbalanced bone remodeling.

摘要

骨质疏松症是一种常见疾病,尤其在老年人中更为常见。本研究旨在全面研究免疫微环境在骨质疏松症发病机制中的作用。使用 GSE35959、GSE7158 和 GSE13850 数据集的表达谱分析差异表达,并鉴定与免疫特征相关的枢纽基因。基于一名骨质疏松症患者的单细胞 RNA 测序 (scRNA-seq) 数据,对不同细胞类型进行分类,并探讨免疫环境与骨质疏松症之间的关系。选择了 12 个与免疫特征显著相关的枢纽基因,并使用 scRNA-seq 数据定义了 11 个亚组。在间充质干细胞 (MSCs) 向成骨细胞转化的过程中,两个枢纽基因 (CDKN1A 和 TEFM) 的表达发生了显著改变。趋化因子和趋化因子受体在不同细胞类型中存在差异富集。CXCL12 在 MSCs 中高表达。本研究强调了免疫微环境在骨质疏松症发病机制中的关键作用。趋化因子和趋化因子受体可以调节细胞发育,影响不同细胞类型之间的相互作用,导致骨重建失衡。

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