JAK/STAT signaling promotes the emergence of unique cell states in ulcerative colitis

• DOI: 10.1016/j.stemcr.2024.06.006
• Publication Date: 2024-07-18T14:39:51Z
• Authors: Grzegorz Maciag; Stine Lind Hansen; Kata Krizic; Lauge Kellermann; Maureen Joy Inven...; Svetlana Ulyanchenko; Martti Maimets; Astrid Møller Baa...; Lene Buhl Riis; Konstantin Khodos...; Toshiro Sato; Raul Bardini Bressan; Ole Haagen Nielsen; Kim B. Jensen
• Keywords: Cell Signaling; Intestinal epithelium; Cell fate determination

The intestinal epithelium ensures uptake of vital nutrients and acts as a barrier between luminal contents the underlying immune system. In inflammatory bowel diseases, such ulcerative colitis (UC), this is compromised, patients experience debilitating symptoms. Here, we perform single-cell RNA profiling epithelial cells outline patterns cell fate decisions in healthy individuals UC patients. We demonstrate that hierarchical behavior are altered identify unique cellular states associated with Janus kinase/signal transducer activator transcription (JAK/STAT) activation ulcerated non-ulcerated areas colonic epithelium. These transcriptional changes could be recapitulated human organoids, wherein cytokine-mediated JAK/STAT led to emergence populations augmented regenerative properties. Altogether, our findings indicate intricate relationships cytokine signaling regulate during tissue regeneration humans have important implications for understanding biology.