MRC - Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Liverpool, UK.
Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, The University of Liverpool, Leahurst Campus, Neston, CH64 7TE, UK.
Sci Rep. 2017 Oct 31;7(1):14443. doi: 10.1038/s41598-017-14650-z.
The development of tendinopathy is influenced by a variety of factors including age, gender, sex hormones and diabetes status. Cross platform comparative analysis of transcriptomic data elucidated the connections between these entities in the context of ageing. Tissue-engineered tendons differentiated from bone marrow derived mesenchymal stem cells from young (20-24 years) and old (54-70 years) donors were assayed using ribonucleic acid sequencing (RNA-seq). Extension of the experiment to microarray and RNA-seq data from tendon identified gender specific gene expression changes highlighting disparity with existing literature and published pathways. Separation of RNA-seq data by sex revealed underlying negative binomial distributions which increased statistical power. Sex specific de novo transcriptome assemblies generated fewer larger transcripts that contained miRNAs, lincRNAs and snoRNAs. The results identify that in old males decreased expression of CRABP2 leads to cell proliferation, whereas in old females it leads to cellular senescence. In conjunction with existing literature the results explain gender disparity in the development and types of degenerative diseases as well as highlighting a wide range of considerations for the analysis of transcriptomic data. Wider implications are that degenerative diseases may need to be treated differently in males and females because alternative mechanisms may be involved.
肌腱病的发展受到多种因素的影响，包括年龄、性别、性激素和糖尿病状态。对转录组数据的跨平台比较分析阐明了这些实体在衰老背景下的联系。使用核糖核酸测序 (RNA-seq) 对来自年轻（20-24 岁）和年老（54-70 岁）供体的骨髓间充质干细胞分化的组织工程肌腱进行了检测。将实验扩展到肌腱的微阵列和 RNA-seq 数据，确定了性别特异性基因表达变化，突出了与现有文献和已发表途径的差异。通过性别对 RNA-seq 数据进行分离揭示了潜在的负二项式分布，这增加了统计能力。性别特异性从头转录组组装产生了较少的较大转录本，其中包含 miRNA、lincRNAs 和 snoRNAs。结果表明，在老年男性中，CRABP2 表达的减少导致细胞增殖，而在老年女性中，它导致细胞衰老。结合现有文献，这些结果解释了退行性疾病在男性和女性中的发展和类型的性别差异，并强调了对转录组数据分析的广泛考虑。更广泛的影响是，退行性疾病可能需要在男性和女性中以不同的方式治疗，因为可能涉及替代机制。
