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Peer-reviewedCC BY 4.0PLOS One

Podocyte injury damages podocytes in chimeric organoids

  1. 1Department of Physiology, Tokai University School of Medicine, Isehara, Japan
  2. 2Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Japan
  3. 3Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

Abstract

We have previously shown that injury to a subset of podocytes can trigger indirect damage in neighboring podocytes, but whether this phenomenon depends on direct intercellular interaction is unknown. To address this, kidney organoids were generated from nephron progenitor cells of two mouse lines: one expressing a receptor for a podocyte-specific immunotoxin and another expressing a tagged ribosomal protein. In chimeric organoids containing a mosaic of these podocyte types, immunotoxin exposure selectively injured the targeted podocytes and also induced indirect injury in adjacent, non-targeted podocytes. This was evidenced by reduced podocin staining and decreased expression of podocyte-specific genes in the non-targeted podocytes. The indirect injury was absent when organoids of each type were cultured separately but in close proximity, indicating that direct cell-to-cell contact within the same glomerular structure is required. These findings show that podocyte injury can propagate locally within kidney organoids, independent of glomerular filtration or other glomerular cell types, and suggest that local podocyte interactions may contribute to the progression of chronic kidney disease.

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BibTeX
@article{udagawa2026podocyte,
  title = {{Podocyte injury damages podocytes in chimeric organoids}},
  author = {Tomohiro Udagawa and Toshikazu Araoka and Kenji Osafune and Taiji Matsusaka},
  journal = {PLOS One},
  year = {2026},
  month = aug,
  doi = {10.1371/journal.pone.0337677},
  url = {https://doi.org/10.1371/journal.pone.0337677},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Podocyte injury damages podocytes in chimeric organoids
AU  - Tomohiro Udagawa
AU  - Toshikazu Araoka
AU  - Kenji Osafune
AU  - Taiji Matsusaka
PY  - 2026
DA  - 2026/08/31
JO  - PLOS One
DO  - 10.1371/journal.pone.0337677
UR  - https://doi.org/10.1371/journal.pone.0337677
AB  - We have previously shown that injury to a subset of podocytes can trigger indirect damage in neighboring podocytes, but whether this phenomenon depends on direct intercellular interaction is unknown. To address this, kidney organoids were generated from nephron progenitor cells of two mouse lines: one expressing a receptor for a podocyte-specific immunotoxin and another expressing a tagged ribosomal protein. In chimeric organoids containing a mosaic of these podocyte types, immunotoxin exposure selectively injured the targeted podocytes and also induced indirect injury in adjacent, non-targeted podocytes. This was evidenced by reduced podocin staining and decreased expression of podocyte-specific genes in the non-targeted podocytes. The indirect injury was absent when organoids of each type were cultured separately but in close proximity, indicating that direct cell-to-cell contact within the same glomerular structure is required. These findings show that podocyte injury can propagate locally within kidney organoids, independent of glomerular filtration or other glomerular cell types, and suggest that local podocyte interactions may contribute to the progression of chronic kidney disease.
SN  - 1932-6203
ER  -