biostudies-literatureBampi GBNIDDK NIH HHSBurroughs Wellcome FundCystic Fibrosis FoundationNHLBI NIH HHSCystic Fibrosis Trust1021-1026https://www.ebi.ac.uk/biostudies/studies/S-EPMC7932027biostudies-literatureUnknown19(6)<h4>Background</h4>Chronic inflammation is a hallmark among patients with cystic fibrosis (CF). We explored whether mutation-induced (F508del) misfolding of the cystic fibrosis transmembrane conductance regulator (CFTR), and/or secondary colonization with opportunistic pathogens, activate tissue remodeling and innate immune response drivers.<h4>Methods</h4>Using RNA-seq to interrogate global gene expression profiles, we analyzed stress response signaling cascades in primary human bronchial epithelia (HBE) and intestinal organoids.<h4>Results</h4>Primary HBE acquired from CF patients with advanced disease and prolonged exposure to pathogenic microorganisms display a clear molecular signature of activated tissue remodeling pathways, unfolded protein response (UPR), and chronic inflammation. Furthermore, CFTR misfolding induces inflammatory signaling cascades in F508del patient-derived organoids from both the distal small intestine and colon.<h4>Conclusion</h4>Despite the small patient cohort size, this proof-of-principle study supports the use of RNA-seq as a means to both identify CF-specific signaling profiles in various tissues and evaluate disease heterogeneity. Our global transcriptomic data is a useful resource for the CF research community for analyzing other gene expression sets influencing CF disease signature but also transcriptionally contributing to CF heterogeneity.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis SocietyGlobal assessment of the integrated stress response in CF patient-derived airway and intestinal tissues.PMC7932027R01 DK068196SRC011K99 HL151965R01 HL136414Bampi GBBijvelds MJCRauscher RFrizzell RAde Jonge HRSorscher EJOliver KEWagner JIgnatova ZKirchner SSantos LAfalseGlobal assessment of the integrated stress response in CF patient-derived airway and intestinal tissues.<h4>Background</h4>Chronic inflammation is a hallmark among patients with cystic fibrosis (CF). We explored whether mutation-induced (F508del) misfolding of the cystic fibrosis transmembrane conductance regulator (CFTR), and/or secondary colonization with opportunistic pathogens, activate tissue remodeling and innate immune response drivers.<h4>Methods</h4>Using RNA-seq to interrogate global gene expression profiles, we analyzed stress response signaling cascades in primary human bronchial epithelia (HBE) and intestinal organoids.<h4>Results</h4>Primary HBE acquired from CF patients with advanced disease and prolonged exposure to pathogenic microorganisms display a clear molecular signature of activated tissue remodeling pathways, unfolded protein response (UPR), and chronic inflammation. Furthermore, CFTR misfolding induces inflammatory signaling cascades in F508del patient-derived organoids from both the distal small intestine and colon.<h4>Conclusion</h4>Despite the small patient cohort size, this proof-of-principle study supports the use of RNA-seq as a means to both identify CF-specific signaling profiles in various tissues and evaluate disease heterogeneity. Our global transcriptomic data is a useful resource for the CF research community for analyzing other gene expression sets influencing CF disease signature but also transcriptionally contributing to CF heterogeneity.2020-01-01T00:00:00Z2020 Nov2024-11-21T00:57:57.792Z2021-03-07T08:15:50ZS-EPMC79320273245120410.1016/j.jcf.2020.04.005