Open AccessSingle-nuclear transcriptomics reveals diversity of proximal tubule cell states in a dynamic response to acute kidney injury
Author(s) -
Louisa M. S. Gerhardt,
Jing Liu,
Kari Koppitch,
Pietro E. Cippà,
Andrew P. McMahon
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2026684118
Subject(s) - acute kidney injury , kidney disease , kidney , medicine , biology , pathology , cancer research
Significance A single acute kidney injury event increases the risk of progression to chronic kidney disease (CKD). Combining single-nucleus RNA sequencing with genetic tracing of injured proximal tubule cells identified a spatially dynamic, evolving injury response following ischemia–reperfusion injury. Failed proximal tubule repair leads to the persistence of a profibrotic, proinflammatoryVcam1 + /Ccl2 + cell type exhibiting a senescence-associated secretory phenotype and a marked transcriptional activation of NF-κB and AP-1 pathway signatures, but no signs of G2 /M cell cycle arrest. Insights from this study can inform strategies to improve renal repair and prevent CKD progression.