Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development [mouse scRNA-seq]

Mammalian kidneys maintain fluid homeostasis through the cellular activity of nephrons and the conjoined collecting system. Each epithelial network originates from distinct progenitor cell populations that reciprocally interact during development. To extend our understanding of human and mouse kidney development, we profiled chromatin organization (ATAC-seq) and gene expression (RNA-seq) in developing human and mouse kidneys. Data were analyzed at a species level and then integrated into a common, cross-species multimodal data set. Comparative analysis of cell types and developmental trajectories identified conserved and divergent features of chromatin organization and linked gene activity, revealing species- and cell-type specific regulatory programs. Identification of human-specific enhancer regions linked through GWAS studies to kidney disease highlights the potential of developmental modeling to provide clinical insight. C57BL6/J mice pups were harvested at day of birth (postnatal day 0) and sexed by urogenital track.哺乳动物肾脏通过肾单位（nephron）的细胞活动及相连的集合系统维持体液稳态。每一个上皮网络均起源于发育过程中相互交互的不同祖细胞群。为深化对人类与小鼠肾脏发育的认知，我们对发育中的人类及小鼠肾脏的染色质组织（ATAC-seq）与基因表达（RNA-seq）进行了测序分析。研究首先按物种层级开展数据分析，随后整合为统一的跨物种多模态数据集。通过对细胞类型与发育轨迹的比较分析，我们鉴定出染色质组织与关联基因活性的保守特征与分化特征，揭示了物种及细胞类型特异性的调控程序。通过全基因组关联研究（Genome-Wide Association Study, GWAS）证实与肾脏疾病相关的人类特异性增强子区域的发现，凸显了发育建模为临床研究提供见解的潜力。本研究选取出生当日（出生后第0天）的C57BL6/J小鼠幼崽，通过泌尿生殖道鉴定其性别。