Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA251661 | ENA |
REPOSITORIES: ENA
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Project description:To identify genes selectively expressed in the DMH, we collected RNA samples from four hypothalamic nuclei, namely the Arc, VMH, DMH and LH, using laser microdissection and conducted microarray analysis to compare their gene expression profiles. The Arc, VMH, DMH, and LH were dissected from C57BL/6 females at 3 month of age by laser microdissection using the Leica 6000 system (n=2 each group).
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Project description:To identify genes selectively expressed in the DMH, we collected RNA samples from four hypothalamic nuclei, namely the Arc, VMH, DMH and LH, using laser microdissection and conducted microarray analysis to compare their gene expression profiles.
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Project description:Identification of genes enriched in Nkx2-1-positive neurons in the Arc, VMH, and DMH of adult mice
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Project description:The hypothalamus (HYP) underlies basal endocrine, physiological, and behavioral drives which inherently differ across species and sexes—ranging from growth and puberty to appetite and metabolism to social behavior. Especially in the rodent brain, these sex-differentiated functions correspond to differences in the volume, cell types, and gene expression of distinct HYP subareas. Recent studies have elucidated the transcriptional profile of single cells in the rodent ventromedial hypothalamus (VMH) and arcuate (ARC), which influence appetitive/social behaviors and growth/metabolism, respectively. However, there is a paucity of studies examining the molecular architecture of the adult human HYP, and transcriptional sex differences in the human VMH and ARC have not been characterized in single-cell or spatial contexts. Using 10x Genomics Visium and Xenium platforms, we generated a multimodal, spatially-resolved molecular atlas of human postmortem VMH and ARC from male and female adult donors. Sex-differential gene expression analysis within these regions revealed correlated autosomal expression differences, with stronger overall sex effects in the ARC. We then leveraged the single-cell-resolution of Xenium to localize sex-differential expression to cell types, finding most occur in ESR1- and KISS1-expressing neurons of the ARC. Finally, we investigated VMH and ARC gene expression in relation to genes associated with neuropsychiatric diseases, identifying a striking enrichment of genes upregulated in the male VMH for known and candidate risk genes for autism spectrum disorders. This work provides a multisample view of the human VMH and ARC in young/middle adulthood across both sexes, including data at both transcriptome-wide and single-cell resolutions, the first single-cell transcriptional atlas of molecular sex differences in the adult human VMH and ARC, and highlights potential sex-differentiated roles for VMH and ARC in neurobehavioral disorders.
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Project description:The hypothalamus (HYP) underlies basal endocrine, physiological, and behavioral drives which inherently differ across species and sexes—ranging from growth and puberty to appetite and metabolism to social behavior. Especially in the rodent brain, these sex-differentiated functions correspond to differences in the volume, cell types, and gene expression of distinct HYP subareas. Recent studies have elucidated the transcriptional profile of single cells in the rodent ventromedial hypothalamus (VMH) and arcuate (ARC), which influence appetitive/social behaviors and growth/metabolism, respectively. However, there is a paucity of studies examining the molecular architecture of the adult human HYP, and transcriptional sex differences in the human VMH and ARC have not been characterized in single-cell or spatial contexts. Using 10x Genomics Visium and Xenium platforms, we generated a multimodal, spatially-resolved molecular atlas of human postmortem VMH and ARC from male and female adult donors. Sex-differential gene expression analysis within these regions revealed correlated autosomal expression differences, with stronger overall sex effects in the ARC. We then leveraged the single-cell-resolution of Xenium to localize sex-differential expression to cell types, finding most occur in ESR1- and KISS1-expressing neurons of the ARC. Finally, we investigated VMH and ARC gene expression in relation to genes associated with neuropsychiatric diseases, identifying a striking enrichment of genes upregulated in the male VMH for known and candidate risk genes for autism spectrum disorders. This work provides a multisample view of the human VMH and ARC in young/middle adulthood across both sexes, including data at both transcriptome-wide and single-cell resolutions, the first single-cell transcriptional atlas of molecular sex differences in the adult human VMH and ARC, and highlights potential sex-differentiated roles for VMH and ARC in neurobehavioral disorders.
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Project description:Obesity occurs when energy expenditure is outweighed by food intake. Tuberal hypothalamic nuclei, including the arcuate nucleus (ARC), ventromedial nucleus (VMH), and dorsomedial nucleus (DMH), regulate feeding amount as well as energy expenditure. Here we report that mice lacking circadian nuclear receptors REV-ERBa and b in the tuberal hypothalamus (HDKO) gain excessive weight on an obesogenic diet due both to decreased energy expenditure and increased food consumption during the light phase. Moreover, rebound food intake after fasting is markedly increased in HDKO mice. Integrative transcriptomic and cistromic analyses revealed that such disruption in feeding behavior is due to perturbed REV-ERB-dependent leptin signaling in the ARC. Indeed, in vivo leptin sensitivity is impaired in HDKO mice on an obesogenic diet in a circadian manner. Thus, REV-ERBs play a crucial role in hypothalamic regulation of food intake and circadian leptin sensitivity in diet-induced obesity.
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Project description:Obesity occurs when energy expenditure is outweighed by food intake. Tuberal hypothalamic nuclei, including the arcuate nucleus (ARC), ventromedial nucleus (VMH), and dorsomedial nucleus (DMH), regulate feeding amount as well as energy expenditure. Here we report that mice lacking circadian nuclear receptors REV-ERBa and b in the tuberal hypothalamus (HDKO) gain excessive weight on an obesogenic diet due both to decreased energy expenditure and increased food consumption during the light phase. Moreover, rebound food intake after fasting is markedly increased in HDKO mice. Integrative transcriptomic and cistromic analyses revealed that such disruption in feeding behavior is due to perturbed REV-ERB-dependent leptin signaling in the ARC. Indeed, in vivo leptin sensitivity is impaired in HDKO mice on an obesogenic diet in a circadian manner. Thus, REV-ERBs play a crucial role in hypothalamic regulation of food intake and circadian leptin sensitivity in diet-induced obesity.
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