Project description:Background: There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. Methods: In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. We targeted two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements. Results: Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition. Conclusions: These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.
Project description:BackgroundThere are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.ResultsSites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition.ConclusionsThese results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.
Project description:Quiescent satellite cells, also known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle upon injury throughout life. Although they mainly originate from multipotent stem/progenitors of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb-1 (Mib1) expression in myofibers at puberty, which activates Notch signaling in cycling juvenile satellite cells and causes them to be converted into quiescent adult satellite cells. Myofibers lacking Mib1 failed to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Genetic and inhibitor studies revealed that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofiber niche. Our data show how sex hormones establish quiescent adult satellite cell populations by regulating the myofiber niche at puberty.
Project description:Quiescent satellite cells, also known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle upon injury throughout life. Although they mainly originate from multipotent stem/progenitors of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb-1 (Mib1) expression in myofibers at puberty, which activates Notch signaling in cycling juvenile satellite cells and causes them to be converted into quiescent adult satellite cells. Myofibers lacking Mib1 failed to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Genetic and inhibitor studies revealed that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofiber niche. Our data show how sex hormones establish quiescent adult satellite cell populations by regulating the myofiber niche at puberty. Microarray analysis of Veh or DHT-injected 10-day-old mice s.c. injected with Veh or DHT. TA muscles were isolated 24 h after the injection.
Project description:AIRE expression in thymus is downregulated by estrogen after puberty, what probably renders women more susceptible to autoimmune disorders. Here we investigated the effects of minipuberty on male and female infant human thymic tissue in order to verify if this initial transient increase in sex hormones - along the first six months of life - could affect thymic transcriptional network regulation and AIRE expression. Gene co-expression network analysis for differentially expressed genes and miRNA-target analysis revealed sex differences in thymic tissue during minipuberty, but such sex differences were not detected in thymic tissues from donors aged 7-18 moths of age, the non-puberty group. AIRE expression was essentially the same in both sexes in minipuberty and in non-puberty groups, as assessed by genomic and immunohistochemical assays. However, AIRE-interactors networks showed several differences in all groups regarding gene-gene expression correlation. Therefore, minipuberty and genomic mechanisms interact in shaping thymic sexual dimorphism along the first six moths of life.
Project description:AIRE expression in thymus is downregulated by estrogen after puberty, what probably renders women more susceptible to autoimmune disorders. Here we investigated the effects of minipuberty on male and female infant human thymic tissue in order to verify if this initial transient increase in sex hormones - along the first six months of life - could affect thymic transcriptional network regulation and AIRE expression. Gene co-expression network analysis for differentially expressed genes and miRNA-target analysis revealed sex differences in thymic tissue during minipuberty, but such sex differences were not detected in thymic tissues from donors aged 7-18 moths of age, the non-puberty group. AIRE expression was essentially the same in both sexes in minipuberty and in non-puberty groups, as assessed by genomic and immunohistochemical assays. However, AIRE-interactors networks showed several differences in all groups regarding gene-gene expression correlation. Therefore, minipuberty and genomic mechanisms interact in shaping thymic sexual dimorphism along the first six moths of life.
Project description:AIRE expression in thymus is downregulated by estrogen after puberty, what probably renders women more susceptible to autoimmune disorders. Here we investigated the effects of minipuberty on male and female infant human thymic tissue in order to verify if this initial transient increase in sex hormones - along the first six months of life - could affect thymic transcriptional network regulation and AIRE expression. Gene co-expression network analysis for differentially expressed genes and miRNA-target analysis revealed sex differences in thymic tissue during minipuberty, but such sex differences were not detected in thymic tissues from donors aged 7-18 moths of age, the non-puberty group. AIRE expression was essentially the same in both sexes in minipuberty and in non-puberty groups, as assessed by genomic and immunohistochemical assays. However, AIRE-interactors networks showed several differences in all groups regarding gene-gene expression correlation. Therefore, minipuberty and genomic mechanisms interact in shaping thymic sexual dimorphism along the first six moths of life.
Project description:This project investigates immune response differences in male and female during puberty. Experiment Overall Design: The specific aim is to expression profile of mouse male and femail spleens at pre-puberty (3-4 week old), puberty (6-9 week old), and post-puberty (24-28 week old).
Project description:Muscle-specific populations of proprioceptive sensory neurons form selective connections with spinal motor neurons, implying the existence of molecular distinctions between proprioceptor subpopulations. Here, we compare the gene expression profiles of proprioceptors that supply an antagonistic muscle pair functioning at a single hindlimb joint.
Project description:Muscle-specific populations of proprioceptive sensory neurons form selective connections with spinal motor neurons, implying the existence of molecular distinctions between proprioceptor subpopulations. Here, we compare the gene expression profiles of proprioceptors that supply an antagonistic muscle pair functioning at a single hindlimb joint.