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Single-nuclear transcriptomics reveals diversity of proximal tubule cell states in a dynamic response to acute kidney injury

2021; National Academy of Sciences; Volume: 118; Issue: 27 Linguagem: Inglês

10.1073/pnas.2026684118

1091-6490

Louisa M.S. Gerhardt, Jing Liu, Kari Koppitch, Pietro E. Cippà, Andrew P. McMahon,

Immune cells in cancer

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, proinflammatory Vcam1 + / 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 G 2 /M cell cycle arrest. Insights from this study can inform strategies to improve renal repair and prevent CKD progression.