Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease
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.
Authors
- Andrew P. McMahon (ORCID: https://orcid.org/0000-0002-3779-1729)
- Matt Thomson (ORCID: https://orcid.org/0000-0003-1021-1234)
- Shiwei Zheng (ORCID: https://orcid.org/0000-0001-6682-6743)
- Guo‐Cheng Yuan (ORCID: https://orcid.org/0000-0002-2283-4714)
- Henry Amrhein (ORCID: https://orcid.org/0000-0002-4264-140X)
- Kari Koppitch (ORCID: https://orcid.org/0009-0007-3314-5651)
- B Wold (ORCID: https://orcid.org/0000-0003-3235-8130)
- Louisa M.S. Gerhardt (ORCID: https://orcid.org/0000-0003-3052-1563)
- Long Cai (ORCID: https://orcid.org/0000-0002-7154-5361)
- Michal Polonsky (ORCID: https://orcid.org/0000-0003-3871-460X)
- Katsuya Lex Colón
- Jina Yun (ORCID: https://orcid.org/0000-0002-7792-3749)
Institutions
- University of Southern California (US)
- California Institute of Technology (US)
- Heidelberg University (DE)
- Broad Center (US)
- University Medical Centre Mannheim (DE)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1038/s41467-024-51186-z
- Citations
- 42
- Primary Topic
- Renal and related cancers
- Type
- article
- Field-Weighted Citation Impact
- 9.82
Funders
- University of Southern California
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases