Abstract
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.
Highlights
Summary data for RNA-seq samples from TET (E-MTAB-4879), tendon (E-MTAB-2449), and their associated attributes are shown in Tables M1S1 and M2S2
E-MTAB-2449 RNA samples from tendon tissues were processed by Peffers using the same methods and equipment as tissue engineered tendon described in[55]
Young TET and old tendon samples were available for females
Summary
The research aimed to investigate the effects of ageing on the transcription of genes in tendon tissues. TET samples were differentiated as described in[64], sense strand RNA libraries were prepared and sequenced as described in[65] and[66]. Studies for incorporation in the analysis were identified by filtering by organism (Homo sapiens), experiment type (RNA assay) and constructing search queries in array express (Table 11). For comparative purposes the number of tendon studies returned without age or gender specifications are recorded. No gene expression studies assessing TET from humans were publicly available, one study E-MTAB-3732 identified using this search term did not contain age or gender phenotypic data. The filtering process identified only two studies using tendon (E-MTAB-2449 and E-GEOD-26051) where sample attribute columns (sac) age and gender were available (Table 11)
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