Kidney Week 2025 Annual Meeting-Kidney Tissue Genomics Revolution

Video Transcription

Video Summary

The session introduced major advances in kidney tissue genomics and spatial multiomics aimed at explaining why some patients recover after kidney injury while others progress to chronic kidney disease (CKD). Sanjay Jain presented KPMP Kidney Atlas v2.0, a large NIH-funded effort combining human biopsies and mouse time-course models. The atlas includes 353 patients, 709 samples, and ~1.7 million profiled cells, mapping 128 cell types/states and injury trajectories. Technologies include single-cell multiome, spatial transcriptomics, spatial metabolomics, and AI linking molecular patterns to histology. Key findings include conserved fibroblast transitions to inflammatory fibroblasts and myofibroblasts, immune-cell shifts across AKI/CKD, and proximal tubule trajectories from adaptive repair to failed repair. Regulatory factors such as SOX4/SOX9 and loss of metabolic programs (e.g., PCK1-linked gluconeogenesis) were connected to spatial niches and to noninvasive protein biomarkers predictive of severity and progression across multiple external cohorts.<br /><br />Catherine Bull focused on spatial transcriptomics in immune-mediated glomerulonephritis, showing how regional and subcellular-resolution methods (DSP/Visium/Xenium/COSMx) can quantify glomerular heterogeneity, link gene modules (e.g., complement) to clinical features, and support mechanistic validation (e.g., PDGF inhibition). She highlighted computational challenges in cell segmentation and introduced topological data analysis approaches to improve cell calling and enable future 3D reconstructions and spatial proteomics integration.<br /><br />Michael Eden discussed chromatin and regulatory methods (ATAC, DNA methylation, CUT&RUN) within KPMP, demonstrating how multi-omic alignment identifies regulatory elements and predicts transcription-factor activity in space. Katalin Susztak emphasized using genetics to infer causality, prioritizing genes/cell types from large GWAS, and applying single-cell–resolution spatial mapping to define niches and immune microenvironments, including B-cell–rich tertiary lymphoid–like structures associated with worse diabetic kidney disease outcomes, plus emerging foundation-model AI tools.

Asset Subtitle

Moderator(s): Gabriel Loeb, Katherine Xu

Presentation(s):

Kidney Precision Medicine Project (KPMP) Kidney Tissue Atlas 2.0 - Sanjay Jain
Kidney Spatial Transcriptomics in Health and Diseases - Katherine Bull
Chromatin Landscape in Kidney Health and Diseases - Michael Eadon
From Variant to Gene to Function Using Kidney Tissue Genomics - Katalin Susztak

Meta Tag

Date 11/6/2025

Pathway 1 Genetic Diseases and Development

Session ID 507333

Keywords

kidney tissue genomics

spatial multiomics

KPMP Kidney Atlas v2.0

acute kidney injury to CKD progression

single-cell multiome

spatial transcriptomics

spatial metabolomics

AI histology-molecular integration

fibroblast inflammatory transition

myofibroblast differentiation

proximal tubule adaptive vs failed repair

SOX4 SOX9 regulatory factors

PCK1 gluconeogenesis metabolic program loss

immune-mediated glomerulonephritis spatial profiling

GWAS genetics causality and niche mapping