SOX9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys.

ABSTRACT: The steps governing healing with or without fibrosis within the same microenvironment are unclear. After acute kidney injury (AKI), injured proximal tubular epithelial cells activate SOX9 for self-restoration. Using a multimodal approach for a head-to-head comparison of injury-induced SOX9 lineages, we identified a dynamic SOX9 switch in repairing epithelia. Lineages that regenerated epithelia silenced SOX9 and healed without fibrosis (SOX9^on-off). By contrast, lineages with unrestored apicobasal polarity maintained SOX9 activity in sustained efforts to regenerate, which were identified as a SOX9^on-on Cadherin6^pos cell state. These reprogrammed cells generated substantial single-cell WNT activity to provoke a fibroproliferative response in adjacent fibrobla

SUBMITTER: Aggarwal S 

PROVIDER: S-EPMC11345873 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature