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Clec3b⁺ fibroblasts are the primary effectors of portal fibrosis following activation via a KLF4/periostin axis

GSE298633 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2026/03/16 Platform GPL24247
Summary
Portal fibrosis, a determinant of progression in virtually all chronic liver diseases, prototypically develops in biliary diseases. Using single-cell RNA sequencing and genetic cell fate tracing in mouse models, we identified Clec3b⁺ fibroblasts as a distinct subset of portal fibroblasts, which rapidly expand after biliary injury and give rise to the bulk portal myofibroblasts. Mechanistic analyses revealed that Clec3b⁺ portal fibroblasts activation is governed by a Krüppel-like factor 4 (KLF4)/periostin (POSTN) axis, i.e., KLF4 directly binds the Postn promoter and represses its transcription in quiescent fibroblasts, whereas after injury, KLF4 is downregulated, which allows POSTN, acting via αvβ5 integrin, to drive portal fibroblast activation and portal fibrosis. Our findings identify Clec3b+ portal fibroblasts as the primary effectors of portal fibrosis and demonstrate that the KLF4/POSTN signaling axis regulates their activation, offering potential therapeutic targets for inhibiting fibrosis in biliary diseases.
Published in
Clec3b⁺ fibroblasts are the primary effectors of portal fibrosis following activation via a KLF4/periostin axis
Lei L, Zhao C, Gao W et al. · Nature communications 2026 · PMID 42056126 · doi:10.1038/s41467-026-72394-9
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Also filed as BioProject PRJNA1270063 and SRA study SRP588933. Searching any of these in the dataset finder brings you back here.

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