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Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE232482 | GEO | 2024/06/20

REPOSITORIES: GEO

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

Project description: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.

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Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development

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

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

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

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Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

Project description:Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species.

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