Cross-sectional transcriptional analysis of the ageing murine heart
File(s)
Published version
Author(s)
Greenig, Matthew
Melville, Andrew
Huntley, Derek
Isalan, Mark
Mielcarek, Michal
Type
Journal Article
Abstract
Cardiovascular disease accounts for millions of deaths each year and is currently the leading cause of mortality worldwide. The ageing process is clearly linked to cardiovascular disease, however, the exact relationship between ageing and heart function is not fully understood. Furthermore, a holistic view of cardiac ageing, linking features of early life development to changes observed in old age, has not been synthesized. Here, we re-purpose RNA-sequencing data previously-collected by our group, investigating gene expression differences between wild-type mice of different age groups that represent key developmental milestones in the murine lifespan. DESeq2’s generalized linear model was applied with two hypothesis6testing approaches to identify differentially-expressed (DE) genes, both between pairs of age groups and across mice of all ages. Pairwise comparisons identified genes associated with specific age transitions, while comparisons across all age groups identified a large set of genes associated with the ageing process more broadly. An unsupervised machine learning approach was then applied to extract common expression patterns from this set of age-associated genes. Sets of genes with both linear and non-linear expression trajectories were identified, suggesting that ageing not only involves the activation of gene expression programs unique to different age groups, but also the re-activation of gene expression programs from earlier ages. Overall, we present a comprehensive transcriptomic analysis of cardiac gene expression patterns across the entirety of the murine lifespan.
Date Issued
2020-09
Date Acceptance
2020-08-14
Citation
Frontiers in Molecular Biosciences, 2020, 7, pp.1-14
ISSN
2296-889X
Publisher
Frontiers Media
Start Page
1
End Page
14
Journal / Book Title
Frontiers in Molecular Biosciences
Volume
7
Copyright Statement
© 2020 Greenig, Melville, Huntley, Isalan and Mielcarek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) http://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
https://www.frontiersin.org/articles/10.3389/fmolb.2020.565530/full
Grant Number
RDF01
RDF01
Subjects
RNAseq
aging
cardiomyocyte
gene expression
genetics
heart
transcriptomics
Publication Status
Published
Article Number
565530
Date Publish Online
2020-09-25