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Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in Rhesus macaque brain

ABSTRACT: Long noncoding RNAs (lncRNAs) mediate important epigenetic regulation in a wide range of biological processes and diseases. We applied comprehensive analyses of RNA-seq and CAGE-seq (cap analysis of gene expression and sequencing) to characterize the dynamic changes in lncRNA expression in rhesus macaque (Macaca mulatta) brain in four representative age groups. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age and sex specificities. Spatiotemporal- and sex-biased changes in lncRNA expression were generally higher than those observed in mRNA expression. A negative correlation between lncRNA and mRNA expression in cerebral cortex was observed and functionally validated. Our findings offer a fresh insight into spatial-, age- and sex-biased changes in lncRNA expression in macaque brain, and suggest that the changes represent a previously unappreciated regulatory system that potentially contributes to brain development and ageing.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE87182 | GEO | 2017/07/06

SECONDARY ACCESSION(S): PRJNA343790

REPOSITORIES: GEO

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Project description:Humans exhibit sex differences in the prevalence and presentation of many psychiatric and neurodevelopmental conditions, including Alzheimer’s disease, autism spectrum disorder (ASD), and schizophrenia; however, the ‘omic’, developmental, and environmental underpinnings of these conditions remain elusive. To illuminate these mechanisms and their interactions, and to identify potential therapies, we need large, sex-specific neurobiological data sets from model organisms whose brains exhibit similar characteristics to those of humans, including comparable sex differences. Among existing models, the rhesus macaque is likely to have the greatest translatability; however, comprehensive analyses of brain sex differences in this species are necessary to demonstrate their relevance to sex-biased human conditions. We present an in-depth investigation of sex differences in the rhesus macaque brain transcriptome (RNA-seq) across 527 samples of 15 regions from 36 free-ranging adult individuals (20F/16M), representing the largest collection of bulk brain gene expression data for this species. We identified hundreds of sex-biased genes throughout the rhesus macaque brain, most of which were shared across regions, suggesting convergent regulatory mechanisms. Similar to studies of human brains, these sex-biased genes are regulated by sex hormones and transcription factors that interact with these hormones, male-biased genes are associated with multiple sex-biased human neurological conditions (e.g., ASD, schizophrenia) and energy metabolism, and female-biased genes are associated with the immune response. We also accurately predicted sex from a relatively small number of genes per region and found that, among genes reported to escape X chromosome inactivation in humans, similar genes are the most predictive of sex both across human tissues and in this dataset. Finally, we demonstrated that sex-biased genes exhibit characteristics that facilitate rapid evolution, including a tendency to be located on the sex chromosomes, more tissue-specific expression, and higher genetic variance for expression. Overall, these findings suggest that the rhesus macaque may be an appropriate model for sex-biased human neurological conditions.

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Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in Rhesus macaque brain

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