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Mild dehydration effects on the murine kidney single nucleus transcriptome and chromatin accessibility

ABSTRACT: The kidney is composed of > 40 cell types that work collectively to maintain fluid-electrolyte balance. If not enough fluid is consumed to remain in balance, then vasopressin is released and acts in the kidney to increase water reabsorption. Here the authors used kidney single nucleus multiome-sequencing to determine cell-specific transcriptomes and chromatin accessibility profiles of male and female control (ad libitum water and food) or mildly dehydrated mice (ad libitum food, water deprivation). There were hundreds of sex- and dehydration-specific differentially expressed genes throughout the kidney, most of which did not have a significant change in chromatin accessibility. Thus, even mild dehydration causes cell- and sex-specific transcriptomic changes even though the kidney function to conserve water is the same.

ORGANISM(S): Mus musculus

PROVIDER: GSE232662 | GEO | 2023/10/13

REPOSITORIES: GEO

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Project description:The supraoptic nucleus (SON) of the hypothalamus is an important integrative brain structure that co-ordinates responses to perturbations in water balance and regulates maternal physiology through the release of the neuropeptide hormones vasopressin and oxytocin into the circulation. Both dehydration and lactation evoke a dramatic morphological remodelling of the SON, a process known as function-related plasticity. We hypothesise that some of the changes seen in SON remodelling are mediated by differential gene expression, and have thus used microarrays to document global changes in transcript abundance that accompany chronic dehydration in female rats, and in lactation. In situ hydridisation analysis has confirmed the differential expression of 3 of these genes, namely Tumour necrosis factor induced protein 6, Gonadotrophin inducible transcription factor 1 and Ornithine decarboxylase antizyme inhibitor 1. Comparison of differential gene expression patterns in male and female rats subjected to dehydration and in lactating rats has enabled the identification of common elements that are significantly enriched in gene classes with particular functions. Two of these are related to the requirement for increased protein synthesis and hormone delivery in the physiologically stimulated SON (translation initiation factor activity and endoplasmic reticulum-Golgi intermediate compartment respectively), whilst others are consistent with concept of SON morphological plasticity (collagen fibril organisation, extracellular matrix organization and biogenesis, extracellular structure organization and biogenesis and homophilic cell adhesion). We suggest that the genes co-ordinately regulated in the SON as a consequence of dehydration and lactation form a network that mediates the plastic processes operational in the physiologically activated SON. Each independent microarray sample represented the SON from either 5 female euhydrated, 5 dehydrated (water restriction for 72hours with food ad libitum) or 11 days lactating. In total, 5 microarrays were performed for the Dehydrated and the Lactation groups and 4 for the euhydrated controls. Samples within each group may be considered to be both biological and technical replicates. The GeneSpring-derived MAS5 data described in the publication is not included in this submission.

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Mild dehydration effects on the murine kidney single nucleus transcriptome and chromatin accessibility

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