Project description:Visceral adipose tissue (VAT) is a metabolically active endocrine organ that plays a critical role regulating organismal metabolism. Regulatory T (Treg) cells restrain VAT inflammation, and preserve insulin sensitivity and organismal metabolism. Here we report pronounced sexual dimorphism in VAT Treg cells, which were enriched specifically in males and differed strikingly from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. These differences were imprinted by the adipose tissue in a manner dependent on sex hormones. Male VAT was characterized by heightened inflammation, which resulted in CCR2-dependent recruitment of Treg cells. Sex hormones also regulated the differentiation of unique IL-33-producing stromal cell populations specific to the male VAT, which paralleled the local expansion of Treg cells and the induction of a transcriptional program controlled by transcription factor Blimp1. Overall our findings reveal a novel multi-layered feedback circuit depending on Treg cells and regulated by sex hormones to limit VAT inflammation.
Project description:Visceral adipose tissue (VAT) is a metabolically active endocrine organ that plays a critical role regulating organismal metabolism. Regulatory T (Treg) cells restrain VAT inflammation, and preserve insulin sensitivity and organismal metabolism. Here we report pronounced sexual dimorphism in VAT Treg cells, which were enriched specifically in males and differed strikingly from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. These differences were imprinted by the adipose tissue in a manner dependent on sex hormones. Male VAT was characterized by heightened inflammation, which resulted in CCR2-dependent recruitment of Treg cells. Sex hormones also regulated the differentiation of unique IL-33-producing stromal cell populations specific to the male VAT, which paralleled the local expansion of Treg cells and the induction of a transcriptional program controlled by transcription factor Blimp1. Overall our findings reveal a novel multi-layered feedback circuit depending on Treg cells and regulated by sex hormones to limit VAT inflammation.
Project description:White adipose tissue (WAT) harbors functionally diverse subpopulations of adipose progenitor cells that differentially impact tissue plasticity in a sex- and depot-dependent manner. To date, the molecular basis of this cellular heterogeneity has not been fully defined. Here, we describe a multilayered omics approach to dissect adipose progenitor cell heterogeneity from in three dimensions: progenitor subpopulation, sex, and anatomical localization. We applied state-of-the-art mass spectrometry methods to quantify 4870 proteins in eight different stromal cell populations from perigonadal and inguinal WAT of male and female mice and acquired transcript expression levels of 15477 genes using RNA-seq. Notably, our data highlight the molecular signatures defining sex differences in PDGFR+ preadipocyte differentiation and identify regulatory pathways that functionally distinguish adipose tissue PDGFRb+ subpopulations. The data are freely accessible as a resource at "Pread Profiler. Together, the multilayered omics analysis provides unprecedented insights into adipose stromal cell heterogeneity.
Project description:Genomic imprinting results in the preferential expression of the paternal, or maternal allele of certain genes. We have performed a genome-wide characterization of imprinting in the mouse embryonic and adult brain using F1 hybrid mice generated from reciprocal crosses of CASTEiJ and C57BL/6J mice. We also uncovered genes associated with sex specific parental effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex.
Project description:<p>Cd248 has recently been associated with adipose tissue physiology, demonstrated by reduced weight gain in high fat diet-fed mice with genetic deletion of Cd248 relative to controls. Here we set out to determine the metabolic consequences of loss of Cd248. Strikingly, we find these to be sex specific; By subjecting Cd248-/- and Cd248+/+ mice to a high fat diet and indirect calorimetry study, we identified that only male Cd248-/- mice show reduced weight gain compared to littermate control wildtype mice. In addition, male (but not female) mice showed a lower respiratory exchange ratio on both chow and high fat diets, indicating a predisposition to metabolise lipid. Lipidomic studies on specific fat depots found reduced triglyceride and diglyceride deposition in male Cd248-/- mice, and this was supported by reduced expression of lipogenic and adipogenic genes. Finally, metabolomic analysis of isolated, differentiated preadipocytes found alterations in metabolic pathways associated with lipid deposition in cells isolated from male, but not female, Cd248-/- mice. Overall, our results highlight the importance of sex controls in animal studies and point to a role for Cd248 in sex- and depot-specific regulation of lipid metabolism.</p>
Project description:Genomic imprinting results in the preferential expression of the paternal, or maternal allele of certain genes. We have performed a genome-wide characterization of imprinting in the mouse embryonic and adult brain using F1 hybrid mice generated from reciprocal crosses of CASTEiJ and C57BL/6J mice. We also uncovered genes associated with sex specific parental effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Examination of allele specific expression in the brains of reciprocal crosses of F1 hybrid mice from CASTEiJ and C57BL/6J crosses. Processed data files (GenomicAligned, SNP_calls, TranscriptomeAligned, fRNAdbAligned) and README file linked below as supplementary files.