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

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…

• UD
  U.S. Department of Defense

  Award: KC200178
• AH
  American Heart Association
• AS
  American Society of Nephrology
• CM
  Cedars-Sinai Medical Center
• NI
  National Institutes of Health
• UO
  University of California, Los Angeles
• UO
  University of California, San Diego
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases
• DG
  David Geffen School of Medicine, University of California, Los Angeles
• CA
  Clinical and Translational Science Institute, University of California, Los Angeles
• CD
  Congressionally Directed Medical Research Programs