Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease

Michal Polonsky, Louisa M. S. Gerhardt, Jina Yun, Kari Koppitch, Katsuya Lex Colón, Henry Amrhein, Barbara Wold, Shiwei Zheng, Guo-Cheng Yuan, Matt Thomson, Long Cai () and Andrew P. McMahon ()
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Michal Polonsky: California Institute of Technology
Louisa M. S. Gerhardt: Keck School of Medicine of the University of Southern California
Jina Yun: California Institute of Technology
Kari Koppitch: Keck School of Medicine of the University of Southern California
Katsuya Lex Colón: California Institute of Technology
Henry Amrhein: California Institute of Technology
Barbara Wold: California Institute of Technology
Shiwei Zheng: Icahn School of Medicine at Mount Sinai
Guo-Cheng Yuan: Icahn School of Medicine at Mount Sinai
Matt Thomson: California Institute of Technology
Long Cai: California Institute of Technology
Andrew P. McMahon: Keck School of Medicine of the University of Southern California

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

Abstract: Abstract Kidney injury disrupts the intricate renal architecture and triggers limited regeneration, together with injury-invoked inflammation and fibrosis. Deciphering the molecular pathways and cellular interactions driving these processes is challenging due to the complex tissue structure. Here, we apply single cell spatial transcriptomics to examine ischemia-reperfusion injury in the mouse kidney. Spatial transcriptomics reveals injury-specific and spatially-dependent gene expression patterns in distinct cellular microenvironments within the kidney and predicts Clcf1-Crfl1 in a molecular interplay between persistently injured proximal tubule cells and their neighboring fibroblasts. Immune cell types play a critical role in organ repair. Spatial analysis identifies cellular microenvironments resembling early tertiary lymphoid structures and associated molecular pathways. Collectively, this study supports a focus on molecular interactions in cellular microenvironments to enhance understanding of injury, repair and disease.

Date: 2024
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DOI: 10.1038/s41467-024-51186-z

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