Journal: bioRxiv
Article Title: Cellular and Spatial Drivers of Unresolved Injury and Functional Decline in the Human Kidney
doi: 10.1101/2025.09.26.678707
Figure Lengend Snippet: a. Human kidney samples from healthy reference tissues (HRT), as well as disease tissues associated with AKI and CKD, were processed using one or more assays. The strategy included deep single cell and spatial phenotyping, validations with orthogonal technologies and using analytical methods to delineate spatial contexts of recovery and failed repair. This included pathological staining and assessment, 10X Genomics single nucleus / cell RNA-seq and Multiome (RNA + ATAC), 10X Genomics Visium, Slide-seq2, 10X Xenium, Nanostring CosMx and spatial metabolomics. The atlas demonstrates clinical impact and utility to inform on pathogenetic mechanisms, druggable targets, non-invasive markers that predict clinical outcomes from early injury signatures and the underlying regulatory networks that contribute to AKI progression. Abbreviations: Sex (M = male, F = Female, Unk = unknown); Race (W = white, B = Black, O = other); Age range associated with decade-binned age values per participant. Asterix (other reference tissues including Diabetes Mellitus – Resilient (DM-R) biopsies and reference samples with unknown clinical status. b. Pathways predicted for each disease group in each FTU were grouped into 14 whole cell functions, 8 of which are shown. Heatmaps show the sum of the -log10(p-values) of all pathways annotated to the same whole cell function. ATL/DTL: ascending/descending thin limb, CD: collecting duct, CNT: connecting tubule, DCT: distal convoluted tubule, EC: endothelial cell, FIB: fibroblast, PT: proximal tubule, S: segment, TAL: thick ascending limb, POD: podocyte, PEC: parietal epithelial cell. c. Map of novel druggable targets specific to cell states. Created in BioRender. Jain, S. (2025) https://BioRender.com/rfy8fos . Source data provided.
Article Snippet: CosMx spatial transcriptomics assay was performed on FFPE biopsy tissue sections (5 um) from patients with diabetic nephropathy (n = 3) on a CosMx SMI system under the technology access program by Nanostring technologies.
Techniques: Staining, RNA Sequencing, Cell Function Assay