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

Author

Listed:
  • Michal Polonsky

    (California Institute of Technology)

  • Louisa M. S. Gerhardt

    (Keck School of Medicine of the University of Southern California
    University of Heidelberg)

  • 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)

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.

Suggested Citation

  • 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 & Andrew P. McMahon, 2024. "Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51186-z
    DOI: 10.1038/s41467-024-51186-z
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