Sexual dimorphism in skin immunity is mediated by androgen-ILC2-dendritic cell axis [scRNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE253294 | GEO | 2024/04/09
REPOSITORIES: GEO
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Project description:Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncover a dominant role for type 2 innate lymphoid cells (ILC2) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2 by androgens leads to a reduction in dendritic cell (DC) accumulation and activation in males, and reduced tissue immunity. Collectively, this work uncovers an androgen-ILC2-DC axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set-points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.
2024-04-09 | GSE253293 | GEO
Project description:Gender bias and the role of sex hormones in autoimmune diseases are well established. In specific-pathogen free (SPF) non-obese diabetic (NOD) mice females have 1.3-4.4 times higher incidence of Type 1 diabetes (T1D). Germ-free (GF) mice lose the gender bias (female/male ratio 1.1-1.2). Gut microbiota differed in males and females, a trend reversed by male castration, confirming that androgens influence gut microbiota. Colonization of GF NOD mice with defined microbiota revealed that some but not all lineages overrepresented in male mice supported a gender bias in T1D, and protection did not correlate with androgen levels. However, hormone-supported selective microbial lineage variation may work as a positive feedback mechanism contributing to the sexual dimorphism of autoimmune diseases. Gene expression analysis suggested pathways involved in protection of males from T1D by microbiota.
2013-08-02 | GSE49467 | GEO
Project description:Despite sharing much of their genomes, males and females are often highly dimorphic, reflecting at least in part the resolution of sexual conflict in response to sexually antagonistic selection. Sexual dimorphism arises owing to sex differences in gene expression, and steroid hormones are often invoked as a proximate cause of sexual dimorphism. Experimental elevation of androgens can lead to masculinization of behavior, physiology, and gene expression, but knowledge of the role of hormones remains incomplete, including how the sexes differ in their gene expression in response to exposure to hormones. We addressed these questions in a bird species with a long history of behavioral endocrinological and ecological study, the dark-eyed junco (Junco hyemalis), using a species-specific microarray. Focusing on two brain regions involved in sexually dimorphic behavior and regulation of hormone secretion, we identified 1,639 genes that differed in expression by sex in the ventromedial telencephalon and 768 in hypothalamus. In response to experimentally elevated testosterone, females exhibited a more “male-like” expression pattern than control females; unexpectedly, male expression patterns became more “female-like” rather than hyper-masculinized when compared to control males. This sex difference in pattern arose both because testosterone altered regulation of different genes in each sex and because testosterone altered regulation of the same genes differentially, i.e., up in one sex, down in the other. Hormonally regulated gene expression is a key genetic and physiological mechanism underlying sexual dimorphism, and further study should help to explain how it relates to the resolution of sexual conflict. Hypothalamus: 24 samples were analyzed, all were biological (not technical) replicates. 6 from males treated with testosterone [MT], 6 from control males [MC], 6 from females treated with testosterone [FT], and 6 from control females [FC]. All hybridizations were paired, and all treatment groups were compared, but no sample was analyzed more than once. Ventromedial telencephalon: 24 samples were analyzed, all were biological (not technical) replicates. 6 from males treated with testosterone [MT], 6 from control males [MC], 6 from females treated with testosterone [FT], and 6 from control females [FC]. All hybridizations were paired, and all treatment groups were compared, but no sample was analyzed more than once.
2013-01-30 | E-GEOD-41076 | biostudies-arrayexpress
Project description:The goal of our study was to evaluate at the systems-level, the effect of sex hormones on thymic epithelial cells (TECs). To this end, we sequenced the transcriptome of cortical and medullary TECs (cTECs and mTECs) from three groups of 6 month-old mice: males, females and males castrated at four weeks of age. In parallel, we analyzed variations in the size of TEC subsets in those three groups between 1 and 12 months of age. We report that sex hormones have pervasive effects on the transcriptome of TECs: the number of differentially expressed genes was 1,440 in cTECs and 1,783 in mTECs. Sexual dimorphism was particularly conspicuous in cTECs. Male cTECs displayed low proliferation rates that correlated with low expression of Foxn1 and its main targets. Furthermore, male cTECs expressed relatively low levels of genes instrumental in thymocyte expansion (e.g., Dll4) and positive selection (Psmb11 and Ctsl). Nevertheless, cTECs were more abundant in males than females. Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival and cell differentiation. Unexpectedly, we observed that female and male sex hormones repressed promiscuous gene expression in mTECs. Since sex hormones did not affect the expression of Aire per se, they must impinge on the activity of unidentified regulator(s) of promiscuous gene expression in mTECs. The sexual dimorphism of TECs highlighted here may be mechanistically linked to the well-recognized sex differences in susceptibility to infections and autoimmune diseases.
2015-11-26 | GSE66873 | GEO
Project description:Gender bias and the role of sex hormones in autoimmune diseases are well established. In specific-pathogen free (SPF) non-obese diabetic (NOD) mice females have 1.3-4.4 times higher incidence of Type 1 diabetes (T1D). Germ-free (GF) mice lose the gender bias (female/male ratio 1.1-1.2). Gut microbiota differed in males and females, a trend reversed by male castration, confirming that androgens influence gut microbiota. Colonization of GF NOD mice with defined microbiota revealed that some but not all lineages overrepresented in male mice supported a gender bias in T1D, and protection did not correlate with androgen levels. However, hormone-supported selective microbial lineage variation may work as a positive feedback mechanism contributing to the sexual dimorphism of autoimmune diseases. Gene expression analysis suggested pathways involved in protection of males from T1D by microbiota. We compared gene expression patterns in the pancreatic lymph nodes (PLNs) between four groups of mice (two genders in SPF and GF conditions, respectively). PLNs were isolated from 9-10 week old GF and SPF male and female NOD mice with 3 mice in each group, for a total of 12 samples.
2013-08-02 | E-GEOD-49467 | biostudies-arrayexpress
Project description:Metabolism in males and females is distinct. Differences are usually linked to sexual reproduction, with circulating signals (e.g. hormones) playing major roles. By contrast, sex differences prior to sexual maturity and intrinsic to individual metabolic tissues are less understood. We analyzed Drosophila melanogaster larvae and find that males store more fat than females, the opposite of the sexual dimorphism in adults. We show that metabolic differences are intrinsic to the major fat storage tissue, including many differences in the expression of metabolic genes. Our previous work identified fat storage roles for Spenito (Nito), a conserved RNA-binding protein and regulator of sex determination. Nito knockdown specifically in the fat storage tissue abolished fat differences between males and females. We further show that Nito is required for sex-specific expression of the master regulator of sex determination, Sex-lethal (Sxl). “Feminization” of fat storage cells via tissue-specific overexpression of a Sxl target gene made larvae lean, reduced the fat differences between males and females, and induced female-like metabolic gene expression. Altogether, this study supports a model in which Nito autonomously controls sexual dimorphisms and differential expression of metabolic genes in fat cells in part through its regulation of the sex determination pathway.
2023-04-25 | GSE229991 | GEO
Project description:Despite sharing much of their genomes, males and females are often highly dimorphic, reflecting at least in part the resolution of sexual conflict in response to sexually antagonistic selection. Sexual dimorphism arises owing to sex differences in gene expression, and steroid hormones are often invoked as a proximate cause of sexual dimorphism. Experimental elevation of androgens can lead to masculinization of behavior, physiology, and gene expression, but knowledge of the role of hormones remains incomplete, including how the sexes differ in their gene expression in response to exposure to hormones. We addressed these questions in a bird species with a long history of behavioral endocrinological and ecological study, the dark-eyed junco (Junco hyemalis), using a species-specific microarray. Focusing on two brain regions involved in sexually dimorphic behavior and regulation of hormone secretion, we identified 1,639 genes that differed in expression by sex in the ventromedial telencephalon and 768 in hypothalamus. In response to experimentally elevated testosterone, females exhibited a more “male-like” expression pattern than control females; unexpectedly, male expression patterns became more “female-like” rather than hyper-masculinized when compared to control males. This sex difference in pattern arose both because testosterone altered regulation of different genes in each sex and because testosterone altered regulation of the same genes differentially, i.e., up in one sex, down in the other. Hormonally regulated gene expression is a key genetic and physiological mechanism underlying sexual dimorphism, and further study should help to explain how it relates to the resolution of sexual conflict. Males and females can be highly dimorphic in metabolism and physiology despite sharing nearly identical genomes, and males and females both respond phenotypically to elevated testosterone, a steroid hormone that alters gene expression. Only recently has it become possible to learn how a hormone like testosterone affects global gene expression in non-model systems, and whether it affects the same genes in males and females. To investigate the transcriptional mechanisms by which testosterone exerts its metabolic and physiological effects on the periphery, we compared gene expression by sex and in response to experimentally elevated testosterone in a well-studied bird species, the dark-eyed junco (Junco hyemalis). We identified 324 genes in the liver, and 733 in the pectoralis muscle that were differentially expressed between males and females. In addition, we identified 1,872 genes that were differentially expressed between testosterone-treated and control individuals in at least one tissue and sex. Testosterone-treatment altered the expression of only130 genes in both males and females in the same tissue. These substantial differences in transcriptional response to testosterone suggest that males and females may employ different pathways when responding to elevated testosterone, despite the fact that many phenotypic effects of experimentally elevated testosterone are similar in the sexes. In contrast, of the 130 genes that were affected by testosterone-treatment in both sexes, 78% were regulated in the same direction (e.g. either higher or lower in testosterone-treated than control males and females). Thus, it appears that testosterone acts through both unique and shared transcriptional pathways in males and females, suggesting multiple mechanisms by which sexual conflict can be mediated.
2013-01-30 | GSE41076 | GEO
Project description:Sexual dimorphism of the skeleton is well documented. At maturity, the male skeleton is typically larger and has a higher bone density than the female skeleton. However, the underlying mechanisms for these differences are not completely understood. In this study, we examined sexual dimorphism in the formation of osteoclasts between cells from female and male mice. We found that the number of osteoclasts in bones was greater in females. Similarly, in vitro osteoclast differentiation was accelerated in female osteoclast precursor (OCP) cells. To further characterize sex differences between female and male osteoclasts, we performed gene expression profiling of cultured, highly purified, murine bone marrow OCPs that had been treated for 3 days with M-CSF and RANKL. We found that 125 genes were differentially regulated in a sex-dependent manner. In addition to genes that are contained on sex chromosomes, transcriptional sexual dimorphism was found to be mediated by genes involved in innate immune and inflammatory response pathways. Furthermore, the NFκB-NFATc1 axis was activated earlier in female early osteoclasts, which partially explains the differences in transcriptomic sexual-dimorphism in these cells. Collectively, these findings identify a sex-dependent intrinsic difference in early osteoclasts, which results from an altered response to osteoclastogenic stimulation. In humans these differences could contribute to the lower peak bone mass and increased risk of osteoporosis that females demonstrate relative to males.
2021-05-14 | GSE153299 | GEO
Project description:Sexual dimorphism in mammals, including humans and laboratory rodents, has primarily been attributed to hormonal and sex chromosomal differences. Accumulating evidence now suggests that circadian rhythms also contribute to sexual dimorphism in cardiac physiology and cardiovascular diseases. Here, we show that the circadian transcriptome of the mouse heart exhibits sexual dimorphism. We determined that female hearts express significantly more rhythmically expressed genes (REGs) and that the temporal distribution of the REGs was different between males and females. In addition, the overlap in genes and functional pathways were modest between males and females. All aspects of the sexual dimorphism in the circadian transcriptome was significantly diminished with cardiomyocyte specific loss of the core clock gene, Bmal1. Analysis of all differentially expressed genes (DEGs) between males and females showed that differential expression between sexes was largely diminished with loss of cardiomyocyte Bmal1. We conclude that cardiomyocyte specific Bmal1, and likely the core clock mechanism, plays a vital role in conferring a sexually dimorphic program of gene expression in the adult mouse heart.
2024-12-17 | GSE262714 | GEO
Project description:Hepatocellular carcinoma (HCC) represents the fifth most common form of cancer worldwide and carries a high mortality rate due to lack of effective treatment. Males are eight times more likely to develop HCC that females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28, a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver, with Trim28hep-/- mice displaying sex-specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males. We now demonstrate that obesity and ageing precipitate alterations of TRIM28-dependent transcriptional dynamics, leading to a metabolic infection state responsible for highly penetrant male-restricted hepatic carcinogenesis. Molecular analyses implicate aberrant androgen receptor stimulation, biliary acid disturbances and altered responses to gut microbiota in the pathogenesis of Trim28hep-/--associated HCC. Correspondingly, androgen deprivation markedly attenuates the frequency and severity of tumors, and raising animals under axenic conditions completely abrogates their abnormal phenotype, even upon high-fat diet challenge. This work underpins how discrete polyphenic traits in epigenetically unstable conditions can contribute to a cancer-prone state, and more broadly provides new evidence linking hormonal imbalances, metabolic disturbances, gut microbiota and cancer.
2017-08-22 | GSE86389 | GEO