Longitudinal single-cell multiomic profiling toward elucidating the differential roles of sex and hormones on the molecular programming of the brain
There are many neurological and neuropsychiatric diseases that affect men and women differently, and the reasons for this are not well understood. One factor that may be important is the influence of hormones during puberty, which can cause changes in gene expression that affect how the brain works. Our goal is to investigate the role of sex hormones and genetics in the development of brain diseases that affect men and women differently. To do this will use a mouse model called the four-cores genotype (FCG) to investigate how sex chromosomes and hormones interact to shape gene expression in specific regions of the brain. We will analyze tissue samples from brains of male and female mice with different combinations of sex chromosomes and gonads, using single-nucleus multiomics to profile gene expression and chromatin conformation, analyzing sex-specific effects across different brain regions, and in various cell types within these regions.
We hypothesize that hormonal surges during puberty influence gene transcription in a cell- and brain region-specific manner, and that these changes become embedded in the genome, resulting in sex-specific behaviours. By understanding how hormonal changes interact with genetics to shape brain development, we may be able to identify new targets for interventions to prevent or treat these disorders, and to develop personalized approaches to care that take into account sex-specific differences in disease susceptibility and drug response.
Overall, this research could provide important insights into the complex interactions between genetics, hormones, and brain development that contribute to sex differences in the prevalence of neurological and neuropsychiatric diseases. By identifying the molecular mechanisms underlying these differences, researchers may be able to develop more effective treatments and interventions that account for individual differences in disease risk and response to treatment.
Corina Nagy , Centre de recherche de l’hôpital Douglas/Douglas Hospital Research Centre
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