Shikhar Aggarwal, Zhanxiang Wang, David Rincon Fernandez Pacheco, Anna Rinaldi, Alex Rajewski, Jasper Callemeyn, Elisabet Van Loon, Baptiste Lamarthée, Ambart Ester Covarrubias, Jean Hou, Michifumi Yamashita, Haruhiko Akiyama, S Ananth Karumanchi, Clive N Svendsen, Paul W Noble, Stanley C Jordan, Joshua J Breunig, Maarten Naesens, Pietro E Cippà, Sanjeev Kumar
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 (SOX9on-off ). By contrast, lineages with unrestored apicobasal polarity maintained SOX9 activity in sustained efforts to regenerate, which were identified as a SOX9on-on Cadherin6pos cell state...
February 23, 2024: Science