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Gene expression of Cancer-associated fibroblasts from orthotopically engrafted murine colon tumors on the single cell level (Sort-Seq)

GSE253639 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/07/02 Platform GPL19057
Summary
The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor cells and in cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). While ZEB1 in tumor cells regulates metastasis and therapy resistance, its role in CAFs is largely unknown. Combining fibroblast-specific Zeb1 deletion with immunocompetent mouse models of CRC, we observe that inflammation-driven tumorigenesis is accelerated, whereas invasion and metastasis in sporadic cancers is reduced upon fibroblast-specific loss of Zeb1. Single-cell transcriptomics, histological characterization and in vitro modelling reveal a crucial role in CAF polarization, promoting myofibroblastic features by restricting inflammatory activation. Zeb1 deficiency impairs collagen deposition and CAF barrier function but increasesd NFκB-mediated cytokine production, jointly promoting lymphocyte recruitment and immune checkpoint activation.
Published in
ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer
Menche C, Schuhwerk H, Armstark I et al. · EMBO reports 2024 · PMID 38937629 · doi:10.1038/s44319-024-00186-7
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Also filed as BioProject PRJNA1066384 and SRA study SRP484564. Searching any of these in the dataset finder brings you back here.

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