TY - JOUR
T1 - Multimodal spatial transcriptomic characterization of mouse kidney injury and repair
AU - Xuanyuan, Qiao
AU - Wu, Haojia
AU - Sundaramoorthi, Hemalatha
AU - Isnard, Pierre
AU - Chen, Changfeng
AU - Rahmani, Waleed
AU - Humphreys, Benjamin D.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - The transition from acute kidney injury to chronic kidney disease is characterized by significant changes in the cellular composition and molecular interactions within the kidney. Utilizing high-resolution Xenium and whole transcriptome Visium spatial transcriptomics platforms, we analyze over a million cells on 12 male mouse kidneys across six stages of renal injury and repair. We define and validate 20 major kidney cell populations and delineate distinct cellular neighborhoods through this multimodal spatial analysis. We further reveal a specific fibro-inflammatory niche enriched in failed-repair proximal tubule cells, fibroblasts, and immune cells, with conserved neighborhood gene signatures across mouse and human. Within this niche, we predict Runx2 as a key upstream regulator, along with platelet-derived growth factor and integrin beta-2 signaling pathways shaping the fibrogenic microenvironment. Altogether, our study provides deep insights into the cellular and molecular dynamics during kidney injury and repair and establishes a comprehensive multimodal analytical framework applicable to other spatial omics studies.
AB - The transition from acute kidney injury to chronic kidney disease is characterized by significant changes in the cellular composition and molecular interactions within the kidney. Utilizing high-resolution Xenium and whole transcriptome Visium spatial transcriptomics platforms, we analyze over a million cells on 12 male mouse kidneys across six stages of renal injury and repair. We define and validate 20 major kidney cell populations and delineate distinct cellular neighborhoods through this multimodal spatial analysis. We further reveal a specific fibro-inflammatory niche enriched in failed-repair proximal tubule cells, fibroblasts, and immune cells, with conserved neighborhood gene signatures across mouse and human. Within this niche, we predict Runx2 as a key upstream regulator, along with platelet-derived growth factor and integrin beta-2 signaling pathways shaping the fibrogenic microenvironment. Altogether, our study provides deep insights into the cellular and molecular dynamics during kidney injury and repair and establishes a comprehensive multimodal analytical framework applicable to other spatial omics studies.
UR - https://www.scopus.com/pages/publications/105013175213
U2 - 10.1038/s41467-025-62599-9
DO - 10.1038/s41467-025-62599-9
M3 - Article
C2 - 40813851
AN - SCOPUS:105013175213
SN - 2041-1723
VL - 16
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 7567
ER -