Identification and functional coordination analysis of gene co-expression networks in different tissues of XBP1 cartilage-specific deficient mice

作者全名："Li, Xiaoli; Pan, Yiming; Liu, Kaiwen; Yang, Yuyou; Ye, Yuanlan; Xu, Qingbo; Fan, Mengtian; Guo, Fengjin"

作者地址："[Li, Xiaoli; Pan, Yiming; Liu, Kaiwen; Yang, Yuyou; Ye, Yuanlan; Fan, Mengtian; Guo, Fengjin] Chongqing Med Univ, Sch Basic Med Sci, Dept Cell Biol & Genet, Lab Dev Biol, Chongqing 400016, Peoples R China; [Xu, Qingbo] Kings Coll London, BHF Ctr, Sch Cardiovasc Med & Sci, London, England"

通信作者："Guo, FJ (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Dept Cell Biol & Genet, Lab Dev Biol, Chongqing 400016, Peoples R China."

来源：CELLULAR SIGNALLING

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001102736200001

JCR分区：Q2

影响因子：4.8

年份：2024

卷号：113

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：XBP1; Transcriptome analysis; Co-expressed genes; Cartilage; Brain; Heart; Muscle

摘要："Abnormal differentiation and proliferation of chondrocytes leads to various diseases related to growth and development. The process of chondrocyte differentiation involves a series of complex cellular and molecular interactions. X-box binding protein 1 (XBP1), an essential molecule of the unfolded protein response (UPR) in Endoplasmic Reticulum (ER) stress, participated in cartilage development and causes other related diseases. We previously reported that XBP1 deficiency in cartilage impacts the function and associated diseases of many different tissues including cartilage. However, how differential expression of genes modulates the roles of cartilage and other tissues when XBP1 is lack of in chondrocytes remains unclear. We aimed to screen for differentially expressed (DE) genes in cartilage, brain, heart, and muscle by high-throughput sequencing in XBP1 cartilage-specific knockout (CKO) mice. Further, gene co-expression networks were constructed by weighted gene co-expression network analysis (WGCNA) algorithm and pivot genes were identified in the above four tissues. Protein detection, Hematoxylin-eosin (HE) staining and immunohistochemistry (IHC) experiments have proved that these differentially co-expressed genes participate in the downstream regulatory pathway of different tissues and affect tissue function.Significantly differentially expressed mRNAs [differentially expressed genes (DEGs)] were identified between XBP1 CKO mice and controls in cartilage, brain, heart, and muscle tissues, including 610, 126, 199 and 219 DEGs, respectively. 39 differentially co-expressed genes were identified in the above four tissues, and they were important pivot genes. Comprehensive analysis discovered that XBP1 deficiency in cartilage influences the difference of co-expressed genes between cartilage and other different tissues. These differentially co-expressed genes participate in downstream regulatory pathways of different tissues and affect tissue functions. Collectively, our conclusions may contribute potential biomarkers and molecular mechanisms for the mutual modulation between cartilage and different tissues and the diagnosis and treatment of diseases caused by abnormalities in different tissues. The analysis also provides meaningful insights for future genetic discoveries."

基金机构：National Natural Science Foundation of China [81672209]; Chongqing Science and Technology Bureau [CSTB2022BSXM-JCX0062]; CQMU Program for Youth Innovation in Future Medicine [W0146]

基金资助正文：This work was aided by the National Natural Science Foundation of China (81672209); Chongqing Science and Technology Bureau (CSTB2022BSXM-JCX0062); CQMU Program for Youth Innovation in Future Medicine (W0146).