Spatial Transcriptomics Defines Injury Specific Microenvironments and Cellular Interactions in Kidney Regeneration and Disease

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Sep 5

PMID 39237549

Authors

Michal Polonsky

Louisa M S Gerhardt

Jina Yun

Kari Koppitch

Katsuya Lex Colon

Henry Amrhein

Barbara Wold

Shiwei Zheng

Guo-Cheng Yuan

Matt Thomson

Long Cai

Andrew P McMahon

Affiliations

Soon will be listed here.

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.

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