Pancreatic duct organoid swelling is chloride-dependent

Yunxia O'Malley; Keyan Zarei; Oriana G. Calderon Vanegas; Pratibha Singh; T. Idil Apak; Mitchell Coleman; Ian M. Thornell; Aliye Uc

doi:10.1016/j.jcf.2023.08.003

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Pancreatic duct organoid swelling is chloride-dependent

Journal article

Peer reviewed

Pancreatic duct organoid swelling is chloride-dependent

Yunxia O'Malley, Keyan Zarei, Oriana G. Calderon Vanegas, Pratibha Singh, T. Idil Apak, Mitchell Coleman, Ian M. Thornell and Aliye Uc

Journal of cystic fibrosis, Vol.23(1), pp.169-171

01/2024

DOI: 10.1016/j.jcf.2023.08.003

PMCID: PMC10891289

PMID: 37633792

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10891289/pdf/nihms-1926982.pdfView

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Abstract

Pancreatic secretions become viscous and acidic in Cystic fibrosis (CF), highlighting the role of CFTR in pancreatic fluid and bicarbonate secretion. Forskolin-induced swelling (FIS) assay developed in intestinal organoids measures residual CFTR function. It is not known whether FIS reflects bicarbonate secretion in pancreas, an organ that secretes near-isotonic NaHCO3 levels. To investigate this, we generated pancreatic duct organoids from CF and non-CF pigs. Epithelial and ductal origin was confirmed with epithelial markers, ion transporters and lack of acinar, islet cell markers. CF organoids were small with no identifiable lumen; CFTR was expressed only in non-CF organoids. Utilizing FIS, organoid size increased only in response to chloride, not bicarbonate. This report highlights pancreatic duct organoids isolated for the first time from CF pigs and evidence for chloride and not bicarbonate driving pancreatic organoid swelling. These organoids would be useful to test chloride permeability of CFTR mutations that cause CF pancreatic disease.

Details

Title: Subtitle: Pancreatic duct organoid swelling is chloride-dependent
Creators: Yunxia O'Malley
Keyan Zarei
Oriana G. Calderon Vanegas
Pratibha Singh
T. Idil Apak
Mitchell Coleman
Ian M. Thornell
Aliye Uc
Resource Type: Journal article
Publication Details: Journal of cystic fibrosis, Vol.23(1), pp.169-171
DOI: 10.1016/j.jcf.2023.08.003
PMID: 37633792
PMCID: PMC10891289
NLM abbreviation: J Cyst Fibros
ISSN: 1569-1993
eISSN: 1873-5010
Grant note: DOI: 10.13039/100000002, name: NIH
Language: English
Electronic publication date: 08/24/2023
Date published: 01/2024
Academic Unit: Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Orthopedics and Rehabilitation; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Internal Medicine
Record Identifier: 9984458105502771

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