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

Claudio Novella-Rausell; Magda Grudniewska; Dorien J M Peters; Ahmed Mahfouz

doi:10.1016/j.isci.2023.106877

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

iScience. 2023 May 18;26(6):106877. doi: 10.1016/j.isci.2023.106877. eCollection 2023 Jun 16.

Authors

Claudio Novella-Rausell^{1

2}, Magda Grudniewska², Dorien J M Peters¹, Ahmed Mahfouz^{1

3

4}

Affiliations

¹ Department of Human Genetics, Leiden University Medical Centre, 2333 ZA Leiden, the Netherlands.
² GenomeScan, 2333 BZ Leiden, the Netherlands.
³ Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands.
⁴ Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands.

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.

Keywords: Biological sciences; Cell biology; Transcriptomics.