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

Grzegorz Maciag, Stine Lind Hansen, Kata Krizic, Lauge Kellermann, Maureen Joy Inventor Zøylner, Svetlana Ulyanchenko, Martti Maimets, Astrid Møller Baattrup, Lene Buhl Riis, Konstantin Khodosevich, Toshiro Sato, Raul Bardini Bressan, Ole Haagen Nielsen, Kim B. Jensen

研究成果: Article査読

4 被引用数 (Scopus)

抄録

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

本文言語English
ページ(範囲)1172-1188
ページ数17
ジャーナルStem cell reports
19
8
DOI
出版ステータスPublished - 2024 8月 13

ASJC Scopus subject areas

  • 生化学
  • 遺伝学
  • 発生生物学
  • 細胞生物学

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