A comprehensive mouse kidney atlas enables rare cell population characterization and robust marker discovery

Abstract

The kidney's cellular diversity is on par with its physiological intricacy; yet identifying cell populations and their markers remains challenging. Here, we created a comprehensive atlas of the healthy adult mouse kidney (MKA: Mouse Kidney Atlas) by integrating 140.000 cells and nuclei from 59 publicly available single-cell and single-nuclei RNA-sequencing datasets from eight independent studies. To harmonize annotations across datasets, we built a hierarchical model of the cell populations. Our model allows the incorporation of novel cell populations and the refinement of known profiles as more datasets become available. Using MKA and the learned model of cellular hierarchies, we predicted previously missing cell annotations from several studies. The MKA allowed us to identify reproducible markers across studies for poorly understood cell types and transitional states, which we verified using existing data from micro-dissected samples and spatial transcriptomics.