High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing

Haojia Wu, Eryn E. Dixon, Qiao Xuanyuan, Juanru Guo, Yasuhiro Yoshimura, Chitnis Debashish, Anezka Niesnerova, Hao Xu, Morgane Rouault and Benjamin D. Humphreys ()
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Haojia Wu: Department of Medicine, Washington University in St. Louis School of Medicine
Eryn E. Dixon: Department of Medicine, Washington University in St. Louis School of Medicine
Qiao Xuanyuan: Department of Medicine, Washington University in St. Louis School of Medicine
Juanru Guo: Department of Medicine, Washington University in St. Louis School of Medicine
Yasuhiro Yoshimura: Department of Medicine, Washington University in St. Louis School of Medicine
Chitnis Debashish: 10X Genomics
Anezka Niesnerova: 10X Genomics
Hao Xu: 10X Genomics
Morgane Rouault: 10X Genomics
Benjamin D. Humphreys: Department of Medicine, Washington University in St. Louis School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Emerging spatially resolved transcriptomics technologies allow for the measurement of gene expression in situ at cellular resolution. We apply direct RNA hybridization-based in situ sequencing (dRNA HybISS, Cartana part of 10xGenomics) to compare male and female healthy mouse kidneys and the male kidney injury and repair timecourse. A pre-selected panel of 200 genes is used to identify cell state dynamics patterns during injury and repair. We develop a new computational pipeline, CellScopes, for the rapid analysis, multi-omic integration and visualization of spatially resolved transcriptomic datasets. The resulting dataset allows us to resolve 13 kidney cell types within distinct kidney niches, dynamic alterations in cell state over the course of injury and repair and cell-cell interactions between leukocytes and kidney parenchyma. At late timepoints after injury, C3+ leukocytes are enriched near pro-inflammatory, failed-repair proximal tubule cells. Integration of snRNA-seq dataset from the same injury and repair samples also allows us to impute the spatial localization of genes not directly measured by dRNA HybISS.

Date: 2024
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DOI: 10.1038/s41467-024-45752-8

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