Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease.
Autor: | Polonsky M; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Gerhardt LMS; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.; Fifth Department of Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany., Yun J; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Koppitch K; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA., Colón KL; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Amrhein H; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Wold B; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Zheng S; Department of Genetics and Genomic Sciences and Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Yuan GC; Department of Genetics and Genomic Sciences and Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Thomson M; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Cai L; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. lcai@caltech.edu., McMahon AP; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA. amcmahon@med.usc.edu. |
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Jazyk: | angličtina |
Zdroj: | Nature communications [Nat Commun] 2024 Sep 05; Vol. 15 (1), pp. 7010. Date of Electronic Publication: 2024 Sep 05. |
DOI: | 10.1038/s41467-024-51186-z |
Abstrakt: | 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. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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