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ImmGen report: sexual dimorphism in the immune system transcriptome.

ABSTRACT: Sexual dimorphism in the mammalian immune system is manifested as more frequent and severe infectious diseases in males and, on the other hand, higher rates of autoimmune disease in females, yet insights underlying those differences are still lacking. Here we characterize sex differences in the immune system by RNA and ATAC sequence profiling of untreated and interferon-induced immune cell types in male and female mice. We detect very few differentially expressed genes between male and female immune cells except in macrophages from three different tissues. Accordingly, very few genomic regions display differences in accessibility between sexes. Transcriptional sexual dimorphism in macrophages is mediated by genes of innate immune pathways, and increases after interferon stimulation. Thus, the stronger immune response of females may be due to more activated innate immune pathways prior to pathogen invasion.

SUBMITTER: Gal-Oz ST

PROVIDER: S-EPMC6754408 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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ImmGen report: sexual dimorphism in the immune system transcriptome.

Gal-Oz Shani Talia ST Maier Barbara B Yoshida Hideyuki H Seddu Kumba K Elbaz Nitzan N Czysz Charles C Zuk Or O Stranger Barbara E BE Ner-Gaon Hadas H Shay Tal T

Nature communications 20190920 1

Sexual dimorphism in the mammalian immune system is manifested as more frequent and severe infectious diseases in males and, on the other hand, higher rates of autoimmune disease in females, yet insights underlying those differences are still lacking. Here we characterize sex differences in the immune system by RNA and ATAC sequence profiling of untreated and interferon-induced immune cell types in male and female mice. We detect very few differentially expressed genes between male and female im ...[more]

PMID: 31541153

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Project description:Purpose: To conduct a transcriptomic study of gene oscillations in mouse liver by RNA sequencing of total RNA samples from 6 different time points across the day. Specific interest is to see whether sex is a factor in large scale gene oscillations under ad-libitum control conditions and in response to caloric restriction diet, since caloric restriction was previously reported to affect gene oscillation Methods: Total RNA was isolated from 20 mg mouse liver tissue using mini spin column QIAGEN RNeasy Mini Kit (Ref #74104, Lot#163035346, Hilden, Germany) according to the manufacturer’s protocol. Sample purity was checked on Nano Drop 2000 (Thermo Fisher Scientific, Waltham, MA, USA) with 260/280 ratio ≥ 2.0 and 260/230 ratio ≥ 2.0 for every sample. Each sample used for the analysis had RNA integrity number > 7. The RNA sequencing was performed by Novogene Corporation Inc (Sacramento, CA, USA). After sample quality control, non-directional – polyA enrichment library was prepared using NEBNext Ultra™ II RNA Library Prep Kit for Illumina, and 50M reads (150bp, paired end) per sample were generated on Illumina NovaSeq 6000 platform. RNA-seq reads were mapped to the mouse protein coding genes (Ensembl: Mus_musculus; GRCm38) using Bowtie allowing up to 2-mismatches. The gene expected read counts and Transcripts Per Million (TPM) were estimated by RSEM (v1.2.3). The TPMs were further normalized by EBSeq R package to correct potential batch effect. Results: We have performed RNA sequencing analysis of mouse livers on Ad-libitum and timed Caloric Restriction diet across 6 time points in 24h. The results of subsequent compareRhythms analysis (R package) revealed that circadian rhythms in total RNA liver transcriptome are different between sexes of mice in both the number of oscillating genes and phase under ad-libitum diet. Caloric restriction increased the number of oscillating genes in both sexes and resulted in a larger overlap of rhythmic transcriptome between sexes, but did not eliminate the difference completely. The response of transcriptome to caloric restriction in terms of gain or loss of rhythm in gene expression profiles was also different between sexes. Additionally, we have shown that the lack of data stratification by sex might result in the failure to detect rhythmic changes in expression of some genes. Conclusions: Our study represents the first systematic analysis of the effect of sex on circadian rhythms of liver transcriptome under ad libitum and caloric restriction diets. We have shown that sex based differences exist in rhythmic transcriptome, as well as in the response of rhythmic transcriptome to diet. We are providing the data useful for both circadian and metabolic researchers and point out the gene candidates which may not be identified as rhythmic, if the data is not stratified by sex. With the help of GO analysis we have concluded that sex also influences the preference towards different processes to be regulated in rhythmic manner on transcriptional level - fatty acid metabolism and protein transport in males vs nucleic acid metabolism and RNA processing in females on ad-libitum diet. On calorie-restricted diet nucleic acid metabolism and RNA processing were enriched in males vs protein transport and signal transduction in females on calorie-restricted diet. These findings highlight a complex interaction of sex and diet in their effect on circadian rhythms in liver gene expression. All of the data from sequenced RNA samples from MALE liver were previously uploaded with the GSE211975 dataset. The current dataset only contains RNA-seq samples from FEMALE liver.

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ImmGen report: sexual dimorphism in the immune system transcriptome.

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ImmGen report: sexual dimorphism in the immune system transcriptome.

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