Determining the epigenetic program that generates unique cell types in the kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profiled open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. We show critical reliance of gene expression on distal regulatory elements (enhancers). We define key cell type-specific transcription factors and major gene-regulatory circuits for kidney cells. Dynamic chromatin and expression changes during nephron progenitor differentiation demonstrated that podocyte commitment occurs early and is associated with sustained Foxl1 expression. Renal tubule cells followed a more complex differentiation, where Hfn4a was associated with proximal and Tfap2b with distal fate. Mapping single nucleotide variants associated with human kidney disease identified critical cell types, developmental stages, genes, and regulatory mechanisms. We provide a global single cell resolution view of chromatin accessibility of kidney development. The dataset is available via interactive public websites.

中文翻译：

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小鼠肾脏的单细胞分辨率调节态势突出了细胞分化程序和肾脏疾病靶标

确定在肾脏中生成独特细胞类型的表观遗传程序对于了解组织稳态和损伤反应期间的细胞类型异质性至关重要。在这里，我们在单细胞分辨率下分析了发育中和成年小鼠肾脏中的开放染色质和基因表达。我们显示对远端调控元件（增强子）的基因表达的关键依赖。我们定义了关键细胞类型特异性转录因子和肾细胞的主要基因调控电路。肾单位祖细胞分化过程中动态染色质和表达变化表明足细胞定型发生较早并与持续的Foxl1表达有关。肾小管细胞的分化更加复杂，其中Hfn4a与近端相关，而Tfap2b与远端相关。映射与人类肾脏疾病相关的单核苷酸变异体，确定了关键的细胞类型，发育阶段，基因和调控机制。我们提供肾脏发育的染色质可及性的全球单细胞分辨率视图。该数据集可通过交互式公共网站获得。