Ontology highlight
ABSTRACT:
PROVIDER: PRJNA596441 | ENA |
REPOSITORIES: ENA
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Project description:Sex differences in the brain have been demonstrated in all major vertebrate lineages but are not well understood at a molecular and cellular level. Sex-changing fishes provide a unique opportunity to uncover mechanisms underlying sexual differentiation of the brain and regulation of sexual phenotypes. Sex change requires the complete transformation of the gonads and behaviors, which in turn require transformation of sexually-differentiated control mechanisms in the brain. However, detailed molecular and cellular profiling of sex differences in the brains of sex-changing fish is lacking. In this study we applied single nucleus RNA-sequencing (snRNA-seq) to generate the first atlas of sex differences in preoptic area (POA) and telencephalon of the model anemonefish Amphiprion ocellaris. We uncovered remarkably widespread sex differences in cell-type abundance and cell-type transcriptome. The most prominent difference was observed in the dorsal medial telencephalon where females displayed more than twice as many glutamatergic neurons as males and more than 400 differentially expressed genes consistent with immature neuronal development in males relative to females. These results provide an unparalleled level of depth to our understanding of sexual differentiation in the brain of a sex-changing fish, and richly characterizes numerous specific sexual dimorphisms that must develop during sex change.
2024-08-16 | GSE246731 | GEO
Project description:Estradiol establishes neural sex differences in many vertebrates and modulates mood, behavior, and energy balance in adulthood. In the canonical pathway, estradiol exerts its effects through the transcription factor estrogen receptor α (ERα). While ERα has been extensively characterized in breast cancer, the neuronal targets of ERα, and their involvement in brain sex differences, remain largely unknown. Here we generate a comprehensive map of genomic ERα-binding sites within a sexually dimorphic neural circuit that mediates social behaviors. We conclude that ERα orchestrates sexual differentiation of the mouse brain through two mechanisms: establishing two male-biased neuron types and activating a sustained male-biased gene expression program. Collectively, our findings reveal that sex differences in gene expression are defined by hormonal activation of neuronal steroid receptors. The molecular targets we identify may underlie the effects of estradiol on brain development, behavior, and disease.
2022-04-20 | GSE144706 | GEO
Project description:Sex differences in the developing human brain are primarily attributed to hormonal influence. Recently however, genetic differences and their impact on the developing nervous system have attracted increased attention. To understand genetically driven sexual dimorphisms in neurodevelopment, we investigated genome-wide gene expression in an in vitro differentiation model of male and female human embryonic stem cell lines (hESC), independent of the effects of human sex hormones. Four male and four female-derived hESC lines were differentiated into a population of mixed neurons over 37 days. Differential gene expression and gene set enrichment analyses were conducted on bulk RNA sequencing data. While similar differentiation tendencies in all cell lines demonstrated the robustness and reproducibility of our differentiation protocol, we found sex-biased gene expression already in undifferentiated ESCs at day 0, but most profoundly after 37 days of differentiation. Male and female cell lines exhibited sex-biased expression of genes involved in neurodevelopment, suggesting that sex influences the differentiation trajectory. Interestingly, the highest contribution to sex differences was found to arise from the male transcriptome, involving both Y chromosome and autosomal genes. We propose 13 sex-biased candidate genes (10 upregulated in male cell lines and 3 in female lines) that are likely to affect neuronal development. Additionally, we confirmed gene dosage compensation of X/Y homologs escaping X chromosome inactivation through their Y homologs and identified a significant overexpression of the Y-linked demethylase UTY and KDM5D in male hESC during neuron development, confirming previous results in neural stem cells. Our results suggest that genetic sex differences affect neuronal differentiation trajectories, which could ultimately contribute to sex biases during human brain development.
2024-04-23 | GSE249035 | GEO
Project description:Brain structure and function are sexually dimorphic. As neuroscience research has largely focused on the male brain and behavior, the female brain and, in particular, its inherent dynamics have been left underexplored. During the mammalian reproductive period, the female brain is exposed to fluctuating hormone levels over the cycles known as menstrual (in humans) or estrous (in rodents). Variation in estradiol levels has been shown to affect synaptic plasticity in the female brain, including changes in dendritic spine density systematically across the estrous cycle. Female emotionality and cognitive function vary with physiologically fluctuating sex hormone levels. However, the molecular mechanisms underlying the dynamic nature of the female brain structure and function are currently unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse is dynamic and fluctuates across the estrous cycle. We find changes in chromatin organization associated with the transcriptional activity of nearby genes important for neuronal function, neurotransmission, synapse formation, and behavior. We also link these chromatin dynamics to variation in anxiety-like behavior and to fluctuations in dendritic spine and synaptic density in the ventral hippocampus. In terms of chromatin structure, within-female and between-sex variation are of similar magnitudes, emphasizing the importance of accounting for fluctuating sex-hormone levels in females in the studies of the brain epigenome and behavior. These results provide critical insights into the mechanisms underlying sex-hormone and sex-dependent variation in adult brain structure and function. The study also has implications for better understanding of sex-biased disorders such as depression and anxiety which are strongly associated with sex-hormone status in females and are twice as prevalent in women than in men. This study establishes a foundation for the development of sex-specific approaches to treat sex-biased neuropsychiatric disorders including depression and anxiety disorders.
2019-05-03 | GSE114036 | 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.
2014-06-07 | GSE47798 | GEO
Project description:Sexual dimorphism can evolve through sex-specific regulation of the same gene set. However, sex chromosomes can also facilitate this by directly linking gene expression to sex. Moreover, heteromorphic sex chromosomes often exhibit different gene content, which contributes to sexual dimorphism. Understanding patterns of sex-biased gene expression across organisms is important for gaining insight about the evolution of sexual dimorphism and sex chromosomes. Moreover, studying gene expression in species with recently established sex chromosomes can help understand the evolutionary dynamics of gene loss and dosage compensation. The threespine stickleback is known for its strong sexual dimorphism, especially during the reproductive period. Sex is determined by a young XY sex chromosome pair with three non-recombining regions that have started to degenerate. Using the high multiplexing capability of 3′ QuantSeq to sequence the sex-biased transcriptome of liver, gills and brain, we provide the first characterization of sex-specific transcriptomes from ~80 stickleback (40 males and 40 females) collected from a natural population during the reproductive period. We find that the liver is extremely differentiated (36% of autosomal genes) and reflects ongoing reproduction, while the brain shows very low levels of differentiation (0.78%) with no particular functional enrichment. Finally, the gills exhibit high levels of differentiation (5%), suggesting that sex should be considered in physiological and ecotoxicological studies of gill responses in fishes. We also find that sex-biased gene expression in X-linked genes is mainly driven by a lack of dosage compensation. However, sex-biased expression of genes that have conserved copies on both sex chromosomes is likely driven by the degeneration of Y allele expression and a down-regulation of male-beneficial mutations on the X chromosome.
2024-06-09 | GSE269432 | GEO
Project description:Estradiol establishes neural sex differences in many vertebrates and modulates mood, behavior, and energy balance in adulthood. In the canonical pathway, estradiol exerts its effects through the transcription factor estrogen receptor α (ERα). While ERα has been extensively characterized in breast cancer, the neuronal targets of ERα, and their involvement in brain sex differences, remain largely unknown. Here we generate a comprehensive map of genomic ERα-binding sites within a sexually dimorphic neural circuit that mediates social behaviors. We conclude that ERα orchestrates sexual differentiation of the mouse brain through two mechanisms: establishing two male-biased neuron types and activating a sustained male-biased gene expression program. Collectively, our findings reveal that sex differences in gene expression are defined by hormonal activation of neuronal steroid receptors. The molecular targets we identify may underlie the effects of estradiol on brain development, behavior, and disease.
2022-04-20 | GSE193549 | GEO
Project description:Estradiol establishes neural sex differences in many vertebrates and modulates mood, behavior, and energy balance in adulthood. In the canonical pathway, estradiol exerts its effects through the transcription factor estrogen receptor α (ERα). While ERα has been extensively characterized in breast cancer, the neuronal targets of ERα, and their involvement in brain sex differences, remain largely unknown. Here we generate a comprehensive map of genomic ERα-binding sites within a sexually dimorphic neural circuit that mediates social behaviors. We conclude that ERα orchestrates sexual differentiation of the mouse brain through two mechanisms: establishing two male-biased neuron types and activating a sustained male-biased gene expression program. Collectively, our findings reveal that sex differences in gene expression are defined by hormonal activation of neuronal steroid receptors. The molecular targets we identify may underlie the effects of estradiol on brain development, behavior, and disease.
2022-04-20 | GSE193548 | GEO
Project description:Estradiol establishes neural sex differences in many vertebrates and modulates mood, behavior, and energy balance in adulthood. In the canonical pathway, estradiol exerts its effects through the transcription factor estrogen receptor α (ERα). While ERα has been extensively characterized in breast cancer, the neuronal targets of ERα, and their involvement in brain sex differences, remain largely unknown. Here we generate a comprehensive map of genomic ERα-binding sites within a sexually dimorphic neural circuit that mediates social behaviors. We conclude that ERα orchestrates sexual differentiation of the mouse brain through two mechanisms: establishing two male-biased neuron types and activating a sustained male-biased gene expression program. Collectively, our findings reveal that sex differences in gene expression are defined by hormonal activation of neuronal steroid receptors. The molecular targets we identify may underlie the effects of estradiol on brain development, behavior, and disease.
2022-04-20 | GSE144716 | GEO