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Sox9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys [CUT&Run]

ABSTRACT: Sox9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys [CUT&Run]

PROVIDER: PRJNA1050315 | ENA |

REPOSITORIES: ENA

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Sox9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys [CUT&Run]

Project description:The steps governing healing with or without fibrosis within the same microenvironment are unclear. After acute kidney injury (AKI), the injured proximal tubular epithelial cells activate Sox9 for self-restoration. Using head-to-head comparison of injury- induced Sox9-lineages via spatiotemporal mapping, single-cell sequencing, and single-nuclei chromatin accessibility profiling, we identified a dynamic SOX9 switch. Lineages that regenerated epithelia silenced SOX9 and healed without fibrosis (SOX9on-off). In contrast, lineages that maintained Sox9 activity in attempt to regenerate, demarcated by SOX9-induced Cadherin 6 (SOX9on-on CDH6pos ) cell state, generated single-cell Wnt activity to provoke a fibroproliferative response in adjacent fibroblasts, driving AKI to chronic kidney disease. Transplanted human kidneys displayed similar SOX9/CDH6/WNT2B responses post-injury. Thus, we uncovered a mechanism linking fibrosis to sustained efforts to regenerate the injured tissue.

2024-02-26 | GSE249776 | GEO

Sox9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys

Project description:Sox9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys

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Sox9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys [snATAC-Seq]

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