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

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. Overall design: All are C57BL/6J mice. A male ad lib, a male water deprived, a female ad lib and a female mouse water deprived. Water was removed from the cages of the deprived mice at 3 pm. All sample collection occurred at +/-1 h at midnight (6 hours into the active period of the mice). 630 Female, Ad lib 636 Female, water deprived 638 Male, water deprived 641 Male, Ad lib

肾脏由超过40种细胞类型构成，各类细胞协同维持体液-电解质平衡。若未摄入足够液体以维持稳态，则会释放血管加压素（vasopressin），作用于肾脏以提升水重吸收效率。
本研究中，作者采用肾脏单细胞核多组测序（single nucleus multiome-sequencing）技术，对雄性与雌性对照（自由进食饮水）或轻度脱水小鼠（自由进食、禁水）的细胞特异性转录组与染色质可及性图谱进行检测。
全肾范围内存在数百种兼具性别与脱水特异性的差异表达基因，其中大多数基因的染色质可及性并未发生显著变化。由此可见，即便为轻度脱水，也会引发细胞与性别特异性的转录组改变，尽管肾脏的保水生理功能并未发生变化。
整体实验设计：所有实验对象均为C57BL/6J小鼠，分为4组：雄性自由进食饮水组、雄性禁水组、雌性自由进食饮水组、雌性禁水组。禁水组小鼠的饮水于当日15时（下午3点）移除，所有样本采集均在午夜前后1小时内完成（即小鼠活动周期的第6小时）。具体样本信息如下：
630号：雌性，自由进食饮水；636号：雌性，禁水；638号：雄性，禁水；641号：雄性，自由进食饮水。