CF (1567) vs CFTR-corrected (1566) iPSC-airway at ALI
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ABSTRACT:
PROVIDER: PRJNA838009 | ENA |
REPOSITORIES: ENA
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Project description:To interrogate the intrinsic effect of CFTR on airway epithelium; to interrogate the presence of FOXi1+ASLC3+ ionocyte population. Description of samples:1567 (F508del CF patient of rapid progressive phenotye) and 1566 (isogenic CFTR-repaired pair). iPSC-derived airway epithelium, s/p D15CD47hi/CD26lo sort, 210DCYI media x
2023-03-02 | GSE203007 | GEO
Project description:CF vs CFTR-corrected hiPSC-airway at ALI
| PRJNA838001 | ENA
Project description:CF (1565) vs CFTR-corrected (1564) iPSC_airway at ALI
| PRJNA838010 | ENA
Project description:Platform: iPSC-derived airway plated on 2D-air liquid interface through basal cell intermediate. Purpose of experiment: To examine the role of mutant CFTR on IPSC-derived airway epithelium (ie. immune dysregulation; dysregulated calcium channel signaling etc). Description of samples:Typical phenotype CF F508del (1565) and syngeneic CFTR-corrected (1564) iPSCs- derived airway epithelium at D90 (D15 CD47hi/CD26lo; replated in 3DMG cultured in 210DCIY x 2 weeks, single-cell passaged and cultured in PNExPlus+dual smad media in 3D, s/p 2 NGFR sorts, cultured at air-liquid interface at 2D)
2023-03-02 | GSE203006 | GEO
Project description:CF (1565) vs CFTR-corrected (1564) iPSC-airway at ALI
| PRJNA838008 | ENA
Project description:Purpose of experiment :To 1) evaluate for the presence of pulmonary ionocytes, 2) investigate the role of the CFTR in airway epithelium. Description of samples: 1564 (CF-repaired), 1565 (CF DF508homozygous) iPSC-airway epithelium through basal cell intermediate. iPSC-D15CD47/CD26sort- NGFR sort x 2
2023-03-02 | GSE203008 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-03-02 | GSE203009 | GEO
Project description:Background. Accumulating evidence indicates that CFTR modulators can be effective for CF sufferers. However, in vivo the microRNAs that regulate CFTR are increased in the CF lung milieu and this can nullify the beneficial effects of CFTR modulators. Methods. A panel of target site blockers (TSBs) designed against the CFTR 3’untranslated region (UTR) were tested for their ability to increase CFTR expression by CFTR 3’UTR luciferase assay and western blot. The effect of two lead TSBs on CFTR activity were tested alone or in combination with selected CFTR modulators in four separate p.Phe508del/p.Phe508del in vitro and ex vivo models (CFBE41o-, Cufi-1, primary bronchial epithelial cells, iPSC-derived lung organoids). Respirable poly-lactic-co-glycolic acid (PLGA) nanoparticles encapsulating the TSBs were formulated and tested. Findings. TSBs that target the miR-145-5p or miR-223-3p binding sites at positons 298-305 and 166-173 in the CFTR 3’UTR, respectively, increased CFTR expression and CFTR anion channel activity, and enhance the effects of Lumacaftor/Ivacaftor or Lumacftor/Tezacaftor in CF BECs. PLGAs encapsulating the TSBs promote CFTR expression in primary BECs and retain their biophysical characteristics following nebulization. Interpretation. Alone or in combination with CFTR modulators, CFTR-targeting TSBs encapsulated in PLGA nanoparticles and nebulized to the lung could overcome microRNA-mediated inhibition of CFTR in CF bronchial epithelium. This strategy represents a promising drug-device combination therapy for the treatment for CFTR dysfunction in the lung.
2019-03-27 | GSE128861 | GEO
Project description:Atmospheric oxygen tension is increasingly recognized to be hyperoxic for the maintenance of in vitro cell cultures. Oxygen has broad implications on energy metabolism, cellular growth and many regulatory functions. Primary airway epithelial cells (AECs) differentiated at air-liquid interface (ALI) are the gold standard for preclinical assessment of cystic fibrosis transmembrane conductance regulatory (CFTR) modulator efficacy in CF. The fidelity of CF AECs cultured at atmospheric oxygen tension rather than at reduced oxygen tension which more closely reflect the in vivo environment has not been studied to date. This study examined the impact of ambient (21%) and low (2%) oxygen tension on the expansion and differentiation of nasal epithelial cells (hNECs) derived from 11 participants (8 with CF and 3 non-CF). hNECs expanded under normoxic and chronic hypoxic conditions demonstrated epithelial cobblestone morphology and similar proliferation rate. hNECs differentiated at hypoxia demonstrated poorer differentiation capacity (significantly thinner epithelium and lower TEER) and a shift from ciliated to secretory epithelial phenotype. Hypoxic differentiated hNECs had significantly shorter cilia length, slower beating frequency but had improved cilia coordination. CFTR functional response is altered in hypoxic differentiated hNECs. This study highlights the need to reconsider the oxygen tension used in CF primary cell cultures so as to preserve the characteristics and functional response of the cell models as we progress towards personalised medicine in CF.
2023-03-25 | PXD038893 | Pride
Project description:Cystic fibrosis (CF)-related diabetes (CFRD) is an increasingly common and devastating comorbidity of CF, affecting ~35% of adults with CF. However, the underlying causes of CFRD are unclear. Here, we examined cystic fibrosis transmembrane conductance regulator (CFTR) islet expression and whether the CFTR participates in islet endocrine cell function using murine models of b cell CFTR deletion, and normal and CF human pancreas and islets. Specific deletion of CFTR from murine b cells did not affect b cell function. In human islets, CFTR mRNA was minimally expressed, and CFTR protein/electrical activity was not detected. Isolated CF/CFRD islets demonstrated appropriate insulin and glucagon secretion with few changes in key islet-regulatory transcripts. Furthermore, ~65% of b cell area was lost in CF donors, compounded by pancreatic remodeling and immune infiltration of the islet. These results indicate that CFRD is not caused by intrinsic islet dysfunction from CFTR mutation, but rather, by b cell loss and intra-islet inflammation in the setting of a complex pleiotropic disease
2018-04-25 | GSE110935 | GEO