RNA-seq analysis of chondrocyte transcriptome reveals genetic heterogeneity in LG/J and SM/J murine strains
RNA-seq analysis of chondrocyte transcriptome reveals genetic heterogeneity in LG/J and SM/J murine strains
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DOI：
10.1016/j.joca.2020.01.001
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发表时间：
2020-04-01
影响因子：
7
通讯作者：
Rai, M. F.
中科院分区：
文献类型：
--
作者：
Duan, X.;Cai, L.;Rai, M. F.
目的：研究LG/J(大的，治愈的)和SM/J(小的，非愈合的)小鼠的软骨细胞在转录水平上的差异，试图识别与软骨再生和骨关节炎(OA)易感性有关的分子途径。设计：对LG/J(n=16)和SM/J(n=16)小鼠的软骨细胞进行RNA测序。我们验证了候选基因的表达，并比较了两个小鼠品系之间的单核苷酸多态(SNPs)。我们还检测了耳廓再生的位置候选基因和显示软骨表达差异的长骨长度数量性状基因座(QTL)。结果：我们观察到LG/J和SM/J小鼠品系来源的细胞之间存在明显的遗传异质性。我们发现LG/J软骨细胞富含代表细胞发育、软骨凝聚和细胞分化调控的基因本体论。相反，SM/J软骨细胞中丰富的基因本体论主要与炎症和退变有关。此外，SNP分析表明，在编码区和高度保守的非编码区，LG/J和SM/J之间的多个有效基因的序列存在差异。结论：虽然与细胞分化、软骨发育和软骨凝聚相关的通路的丰富预示着LG/J品系具有良好的愈合能力，但与细胞因子产生、免疫细胞激活和炎症相关的通路的丰富导致SM/J品系对OA的易感性增加。这些数据提供了对软骨细胞转录组的新见解，并有助于识别与单个QTL相关的表型差异背后的数量性状基因和分子差异。(C)2020年国际骨性关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
Objective: To investigate the transcriptomic differences in chondrocytes obtained from LG/J (large, healer) and SM/J (small, non-healer) murine strains in an attempt to discern the molecular pathways implicated in cartilage regeneration and susceptibility to osteoarthritis (OA).Design: We performed RNA-sequencing on chondrocytes derived from LG/J (n = 16) and SM/J (n = 16) mice. We validated the expression of candidate genes and compared single nucleotide polymorphisms (SNPs) between the two mouse strains. We also examined gene expression of positional candidates for ear pinna regeneration and long bone length quantitative trait loci (QTLs) that display differences in cartilaginous expression.Results: We observed a distinct genetic heterogeneity between cells derived from LG/J and SM/J mouse strains. We found that gene ontologies representing cell development, cartilage condensation, and regulation of cell differentiation were enriched in LG/J chondrocytes. In contrast, gene ontologies enriched in the SM/J chondrocytes were mainly related to inflammation and degeneration. Moreover, SNP analysis revealed that multiple validated genes vary in sequence between LG/J and SM/J in coding and highly conserved noncoding regions. Finally, we showed that most QTLs have 20-30% of their positional candidates displaying differential expression between the two mouse strains.Conclusions: While the enrichment of pathways related to cell differentiation, cartilage development and cartilage condensation infers superior healing potential of LG/J strain, the enrichment of pathways related to cytokine production, immune cell activation and inflammation entails greater susceptibility of SM/J strain to OA. These data provide novel insights into chondrocyte transcriptome and aid in identification of the quantitative trait genes and molecular differences underlying the phenotypic differences associated with individual QTLs. (C) 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.