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

2024; American Association for the Advancement of Science; Volume: 383; Issue: 6685 Linguagem: Inglês

10.1126/science.add6371

1095-9203

Shikhar Aggarwal, Zhanxiang Wang, David Rincon Fernandez Pacheco, Anna Maria Rinaldi, Alex Rajewski, Jasper Callemeyn, Elisabet Van Loon, Baptiste Lamarthée, Ambart E. Covarrubias, Jean Hou, M 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,

Pluripotent Stem Cells Research

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