Comprehensive transcriptional landscape of aging mouse liver

BMC Genomics

Research Article

Sheila L. MacRae¹  Mingyan Lin¹  Brandon Milholland¹  Jan Vijg²  Ryan R. White²  Deyou Zheng³ 

[1] Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA;Albert Einstein College of Medicine, Michael F. Price Center for Genetic and Translational Research, 1301 Morris Park Ave, 10461, Bronx, NY, USA;Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA;

关键词: Gene expression;    Aging;    RNA-seq;    Transcriptome;    Non-coding RNA;    Variation;    Liver;   

DOI  :  10.1186/s12864-015-2061-8

 received in 2015-05-27, accepted in 2015-10-10,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundMammalian aging is a highly complex process, a full mechanistic understanding of which is still lacking. One way to help understand the molecular changes underlying aging is through a comprehensive analysis of the transcriptome, the primary determinant of age-related phenotypic diversity. Previous studies have relied on microarray analysis to examine gene expression profiles in different tissues of aging organisms. However, studies have shown microarray-based transcriptional profiling is less accurate and not fully capable of capturing certain intricacies of the global transcriptome.MethodsHere, using directional whole transcriptome RNA-sequencing of aged mouse liver we have identified a comprehensive high-resolution profile of differentially expressed liver transcripts comprised of canonical protein-coding transcripts, transcript isoforms, and non-coding RNA transcripts, including pseudogenes, long non-coding RNAs and small RNA species.ResultsResults show extensive age-related changes in every component of the mouse liver transcriptome and a pronounced increase in inter-individual variation. Functional annotation of the protein-coding mRNAs and isoforms indicated broad alterations in immune response, cell activation, metabolic processes, and RNA modification. Interestingly, multiple lncRNAs (Meg3, Rian, Mirg) from the Dlk-Dio3 microRNA locus were found up-regulated in aging liver, classifying this locus as a putative regulatory hotspot locus in aging liver. Moreover, integration of the altered non-coding RNAs and protein-coding transcripts into interaction networks of age-related change revealed inflammation, cellular proliferation, and metabolism as the dominant aging phenotypes in mouse liver.ConclusionsOur analyses provide the first comprehensive dissection of the transcriptional landscape in aging mouse liver.

【 授权许可】

CC BY   
© White et al. 2015