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Transcriptome analysis of plaque and pWAT immune cells of 16 weeks fed high fat high cholesterol diet LXRa WT and S196A mice.

ABSTRACT: Purpose: The goals of this study is to evaluate the impact of LXRa phosphorylation at S196 in immune cells on atherosclerosi and obesity, on gene expression via RNA-seq. Lab Methods: Bone marrow from LXRa WT and S196A mice was transplanted into Ldlr-/- mice, which were fed a high fat, high cholesterol diet for 16 weeks prior to evaluation of atherosclerosis and obesity. Plaque CD68+ and T cells, and pWAT macrophages and T cells mRNA profiles of LXRa WT and S196A mice were generated by RNA-seq using Illumina HiSeq 2500 (plaque CD68+ samples) or HiSeq 4000 (Plaque T cells and pWAT FBC, FB and T cells samples). Bioinformatics Methods: Quality control and Illumina adapter removal was performed on the raw sequencing output, followed by mapping of each read pair to the GRCm38.96 transcriptome in order to generate the mRNA profile of each sample. Sample groups from different tissues as well as groups from wild-type or mutant samples were compared against each other for differential gene expression. Results: we analyzed genes differentially expressed in plaque LXRa S196A and found that LXRa S196A induced 365 and repressed 205 genes in CD68+ (LogFC > 0.6, p-value < 0.05), and induced 1,578 genes and repressed 2,392 genes in plaque T cells compared to LXRa WT (LogFC > 1, FDR < 0.05). In pWAT, LXRa S196A vs WT analysis showed that LXRa S196A repressed 419 genes and induced 379 genes in FBC, induced 182 genes and repressed 228 genes in FB, and 624 genes were induced and 622 genes were repressed in LXRa WT (LogFC > 1, FDR < 0.05). Conclusions: This study is the first detailed analysis of plaque and pWAT immune cells transcriptomes from LXRa S196A in bone marrow cells of LDLR-/- mice under high fat and high cholesterol diet, generated by RNA-seq. We demonstrated that LXRa S196A is largely affecting transcriptome of immune cells in atherosclerotic plaque and pWAT. The transcriptome remodeling observed is tissue and cell specific, and controls atherosclerosis and obesity progression.

ORGANISM(S): Mus musculus

PROVIDER: GSE162660 | GEO | 2021/01/31

REPOSITORIES: GEO

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Project description:Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic infor- mation. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC sub- group, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differ- ences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male- simple subgroup appears notably different from any geno- mic subgroup so far defined in FBC. Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic infor- mation. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC sub- group, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differ- ences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male- simple subgroup appears notably different from any geno- mic subgroup so far defined in FBC.

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Transcriptome analysis of plaque and pWAT immune cells of 16 weeks fed high fat high cholesterol diet LXRa WT and S196A mice.

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