Analyze the transcriptional signature of kidney glomerular cells in male, female wild-type mice and in female mouse models of estrogen knockout
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE261615 | GEO | 2026/03/01
REPOSITORIES: GEO
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Project description:Estrogen improves insulin sensitivity and increases energy expenditure, contributing to sexual dimorphism regarding type 2 diabetes mellitus (T2DM) susceptibility. Estrogen receptor α (ERα) plays a crucial role in mediating estrogen action on glucose and energy homeostasis. However, the underlying mechanisms remain incompletely understood. Here, we found a ligand-independent effect of ERα on the regulation of glucose homeostasis and identified an ERα-derived peptide as a potential insulin sensitizer. Deficiency of ERα but not ERβ in the liver impaired glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies revealed that ERα promoted hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediated the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we designed a peptide based on ERα 1-280 domain and found that ERα-derived peptide interacted with IRS1, increased IRS1 stability through suppressing its ubiquitination, and enhanced insulin sensitivity. Importantly, administration of ERα-derived peptide into obese mice significantly increased insulin sensitivity, attenuated glucose intolerance, and improved serum lipid profiles. These findings pave the way for the therapeutic intervention of T2DM by targeting the ligand-independent effect of ERα and indicate that ERα-derived peptide is a potential insulin sensitizer for the treatment of T2DM.
2024-04-05 | GSE262841 | 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 of the behaviors or physiological functions in mammals is mainly due to the sex difference of the brain. The goal of this study is to identify genes mediating sexaul dimorphism of the brain. The large-scale analysis with microarray in the present study is an attempt to obtain the candidate gene(s) mediating the perinatal estrogen effect causing the brain sexual differentiation. Thirty female mice were injected with estradiol benzoate (EB) or vehicle on the day of birth, and the hypothalamus was collected at either 1, 3, 6, 12, or 24 h after the EB injection.
2014-06-07 | E-GEOD-47798 | biostudies-arrayexpress
Project description:Stress-related illness represents a major burden on health and society. Understanding the molecular mechanisms underlying stress responses is an important step to understand these diseases, and design treatments. Sexual dimorphism in stress responses have been extensively reported, with depression and most anxiety disorders being more prevalent in women. Corticotrophs of the anterior pituitary play a central role in the generation of hormonal stress responses, by secreting the stress hormone ACTH in response to stressful stimuli. However, their role in contributing to sexually dimorphic responses of the HPA axis is very poorly understood. We performed bulk RNA-sequencing of FACS-sorted corticotrophs from male and female POMC-GFP mice to determine the molecular determinants of sexual dimorphic traits in the activity of these cells, revealing extensive differential gene expression at the transcriptional level. This includes more than 71 mRNAs encoding ion channel subunits, which could be involved in the generation of the sexual dimorphism in their electrical activity.
2023-05-03 | E-MTAB-12885 | biostudies-arrayexpress
Project description:Purpose: While women are more susceptible to pulmonary arterial hypertension (PAH) than men, their right ventricular (RV) function is better preserved. Experimental studies have identified estrogen receptor alpha (ERα) as a likely mediator for estrogen protection in the RV. However, the role of ERα in preserving RV function and remodeling during pressure overload remains poorly understood. We hypothesized that loss of functional ERα removes female protection from adverse remodeling and is permissive for development of a maladapted RV phenotype. Methods: Male and female rats with a loss-of-function mutation in ERα (ERαMut) and wildtype (WT) littermates, while at their surgical plane of anesthesia, underwent RV pressure overload by pulmonary artery banding (PAB) or a sham surgery. Results: At 10 weeks post-PAB, WT and ERαMut demonstrated RV hypertrophy. Single beat analysis and Tau Weiss calculation from RV pressure waveforms (collected during surgical plane of anesthesia) demonstrated uncoupling of the RV-pulmonary vascular circuit and diastolic dysfunction, respectively, in female, but not male, ERαMut PAB rats. Similarly, female, but not male, ERαMut exhibited increased RV fibrosis, comprised primarily of stiffer collagen type I, suggesting RV stiffening by collagen type I accumulation. RNA-sequencing in female WT and ERαMut RV revealed Kallikrein related-peptidase 10 (Klk10) and Jun Proto-Oncogene (Jun) as possible mediators of female RV protection during PAB. Conclusions: ERα in females is protective against RV-pulmonary vascular uncoupling, diastolic dysfunction, and fibrosis in response to pressure overload. ERα appears to be dispensable for RV adaptation in males. ERα may be a mediator of superior RV adaptation in female patients with PAH.
2020-04-11 | GSE148453 | GEO
Project description:We constructed eight libraries of female and male E. pela at different developmental stages using RNA-seq technology. Many genes and pathways related to sexual dimorphism were identified.The female and male E. pela take different developmental patterns. The sexual dimorphism in E. pela may involve many different regulatory components.
2013-11-09 | GSE52228 | GEO
Project description:We constructed eight libraries of female and male E. pela at different developmental stages using RNA-seq technology. Many genes and pathways related to sexual dimorphism were identified.The female and male E. pela take different developmental patterns. The sexual dimorphism in E. pela may involve many different regulatory components. Female and male E. pela at different developmental stages using RNA-seq technology
2013-11-09 | E-GEOD-52228 | biostudies-arrayexpress
Project description:We found that hRPC differentiation capacity contributed to the sexual dimorphism of kidney disorders . To study the mechanisms controlling these differences we characterized the transcriptional signature of hRPC
2026-03-01 | GSE292001 | GEO
Project description:Type III adenylyl cyclase (AC3, ADCY3) is predominantly enriched in neuronal primary cilia throughout the central nervous system (CNS). Genome-wide association studies in humans have associated ADCY3 with major depressive disorder and autistic spectrum disorder, both of which exhibit sexual dimorphism. To date, it is unclear how AC3 affects protein phosphorylation and signal networks in central neurons, and what causes the sexual dimorphism of autism. We employed a mass spectrometry (MS)-based phosphoproteomic approach to quantitatively profile differences in phosphorylation between inducible AC3 knockout (KO) and wild type (WT), male and female mice. In total, we identified 4655 phosphopeptides from 1756 proteins, among which 565 phosphopeptides from 322 proteins were repetitively detected in all samples. Comparison of AC3 KO and WT datasets revealed that phosphopeptides with motifs matching proline-directed kinases’ recognition sites had a lower abundance in the KO dataset than in WTs. We detected 14 phosphopeptides restricted to WT dataset (i.e., from Spast and Ppp1r14a) and 35 exclusively in KOs (i.e., from Sptan1, Arhgap20, Arhgap44, and Pde1b). Moreover, 95 phosphopeptides were identified only in female dataset and 26 only in males. Label-free MS spectrum quantification using Skyline further identified phosphopeptides that had high expression abundance in each sample group. In total, over 200 modifications were gender-biased and had increased expression in females relative to males. 29% gender-biased phosphopeptides were from autism-associated proteins, including Dlg1, Dlg4, Dlgap2, Syn1, Syngap1, Ctnna1, Ctnnd1, Ctnnd2, Pkp4, and Arvcf. These autism proteins were well-connected in protein-protein interaction network that centered around Dlg4. This study provided the first phosphoproteomics evidence, suggesting that gender-biased post-translational phosphorylation may be implicated in the sexual dimorphism of autism.
2019-04-10 | PXD012259 | Pride
Project description:Cardiac myocyte-specific ERalpha KO mice were generated to assess the role of ERα in the heart. Female ERαHKO mice displayed a modest cardiac phenotype, but unexpectedly, an the most striking obesity phenotype developed was obesity in female ERαHKO but not male ERαHKO mice. In female ERαHKO mice we identified cardiac dysfunction, mild glucose and insulin intolerance, and reduced ERα gene expression in skeletal muscle and white adipose tissue (WAT). RNA-seq analysis was conducted on the ventricles and WAT of male and female ERαHKO mice to further elucidate the transcriptomic alterations associated with the shift in metabolic profiles in the tissues of interest.
2023-01-24 | E-MTAB-12564 | biostudies-arrayexpress