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

Autor:	Maciag G; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Hansen SL; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Krizic K; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Kellermann L; Department of Gastroenterology, Herlev Hospital, University of Copenhagen, 2730 Herlev, Denmark., Inventor Zøylner MJ; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Ulyanchenko S; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Maimets M; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Baattrup AM; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Riis LB; Department of Pathology, Herlev Hospital, University of Copenhagen, 2730 Herlev, Denmark., Khodosevich K; Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark., Sato T; Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan., Bressan RB; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: raul.bressan@sund.ku.dk., Nielsen OH; Department of Gastroenterology, Herlev Hospital, University of Copenhagen, 2730 Herlev, Denmark. Electronic address: ohn@dadlnet.dk., Jensen KB; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: kim.jensen@sund.ku.dk.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2024 Aug 13; Vol. 19 (8), pp. 1172-1188. Date of Electronic Publication: 2024 Jul 18.
DOI:	10.1016/j.stemcr.2024.06.006
Abstrakt:	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. Competing Interests: Declaration of interests T.S. is an inventor on several patents related to organoids. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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