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Transcriptomic and functional profiling of human intestinal organoids identifies enhanced calcium signalling and thrombospondin-2 activity in cystic fibrosis

delete2026-06-24
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OA
AI
E
E.C. Slater
W
Woo Jin Yang
N
Nefeli Skoufou-Papoutsaki
S
Stephen A. Renshaw
R
Róisı́n M. Owens
M
Matthias Zilbauer *
DOI:10.1016/j.jcf.2026.06.007delete
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Abstract

Abstract

En 中文
• CRISPR-edited human organoids reliably model intestinal epithelial cells in cystic fibrosis. • CFTR knockout organoids capture disease-related phenotypes at a molecular and functional level. • Loss of CFTR results in elevated Ca2+ flux, which may be associated with a sensitised THBS2 response. • Verapamil provides in vitro protection against elevated Ca2+ and THBS2 in CFTR knockout organoids.
Keywords:
Human intestinal organoids
Cystic fibrosis
CRISPR
Calcium dysregulation
CFTR
WT
Wild-type
KO
Knockout
HIO
Human intestinal organoid
IEO
Intestinal epithelial organoid
CF
Cystic fibrosis
FIS
Forskolin-induced swelling
CRC
Colorectal cancer
SC
Sigmoid colon
DEG
Differentially expressed gene
hDEG
Highly differentially expressed gene
GSEA
Gene-set enrichment analysis
TA
Transit-amplifying
VER
Verapamil
ROS
Reactive oxygen species
TEER
Transepithelial electrical resistance
EMT
Epithelial-to-mesenchymal transition
ROI
Region of interest

Journal

Journal of Cystic Fibrosis cover
Journal of Cystic Fibrosis
IF:
6
Papers:
2.9K
Citations:
7.3K

Organization

U
university of sheffield
Scholars:
2.9K
Papers: 1.4K
Citations: 1
U
university of cambridge
Scholars:
6.8K
Papers: 3.2K
Citations: 3
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