Spatial transcriptional mapping of the human nephrogenic program

Congenital abnormalities of the kidney and urinary tract are among the most common birth defects, affecting 3% of newborns. The human kidney forms around a million nephrons from a pool of nephron progenitors over a 30-week period of development. To establish a framework for human nephrogenesis, we spatially resolved a stereotypical process by which equipotent nephron progenitors generate a nephron anlage, then applied data-driven approaches to construct three-dimensional protein maps on anatomical models of the nephrogenic program. Single-cell RNA sequencing identified progenitor states, which were spatially mapped to the nephron anatomy, enabling the generation of functional gene networks predicting interactions within and between nephron cell types. Network mining identified known developmental disease genes and predicted targets of interest. The spatially resolved nephrogenic program made available through the Human Nephrogenesis Atlas (https://sckidney.flatironinstitute.org/) will facilitate an understanding of kidney development and disease and enhance efforts to generate new kidney structures. [Display omitted] •Mouse and human kidneys undergo a conserved stereotypical developmental program•Transcriptomes were mapped to protein-based developmental models•Data predict lineage relationships in early human nephron development•View lineage and interaction predictions: https://sckidney.flatironinstitute.org/ Lindström et al. show that mouse and human nephrogenesis follow evolutionary conserved and stereotypical programs. Spatial mapping of transcriptional profiles predicts cell intermediates and regulatory interactions at play in development and disease. A web interface facilitates viewing and analysis of these findings.