Cell-intrinsic differences between human airway epithelial cells from children and adults

Hynds, Robert E.; Pennycuick, Adam; Nigro, Ersilia; Gowers, Kate H.C.; Denais, Céline; Goméz-López, Sandra; Lazarus, Kyren A.; Orr, Jessica C.; Pearce, David R.; Clarke, Simon; Lee, Dani Do Hyang; Woodall, Maximillian; Masonou, Tereza; Case, Katie-Marie; Teixeira, Vítor Hugo; Hartley, Benjamin E. J.; Hewitt, Richard; Yaghchi, Chadwan Al; Sandhu, Gurpreet S.; Birchall, Martin A.; O’Callaghan, Christopher; Smith, Claire M.; Coppi, Paolo De; Butler, Colin R.; Janes, Sam M.

doi:10.1016/j.isci.2022.105409

Cited by 10 publications

(13 citation statements)

References 51 publications

(64 reference statements)

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“…Antibody staining of human donor lungs also showed no difference in the abundance of ciliated cells in the intrapulmonary bronchi of infants and adults (Figures S1E and S1F). Taken together, our and previous findings 36,39 show that age has no effect on cellular composition of human bronchial epithelium in vivo or differentiation potentials of BSCs in vitro .…”

Section: Resultssupporting

confidence: 87%

“…As controls, TA BSC lines from adult patients (32-55 years of age) who were intubated due to cardiogenic and neurogenic respiratory failure were similarly derived (Supplementary Table 1) and differentiated in ALI (Figures 1A and 1B). Transcriptome profiling of neonatal and adult TA BSCs identified differentially expressed genes enriched in the cell cycle pathways (Figures S1A-S1C), consistent with differences in BSC proliferation with age 39 . Neonatal and adult TA BSCs exhibited similar differentiation potentials in ALI, evidenced by comparable percentages of all major epithelial cell types between the two ages, including RFX3 + ciliated cell (41.4%±3.1% (neonate) vs 38.7%±1.7% (adult), p=0.53), SCGB1A1 + club cells (10.0%±1.9% (neonate) vs 15.1%±3.9% (adult), p=0.22), MUC5AC + goblet cells (9.7%±2.5% (neonate) vs 10.3%±2.4% (adult), p=0.88), and the remaining TP63 + BSCs (26.1%±3.8% (neonate) vs 27.6%±3.5% (adult), p=0.79) (Figures 1B and S1D).…”

Section: Resultsmentioning

confidence: 56%

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Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells

Zhao,

Wang,

Bai

et al. 2023

Preprint

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Respiratory syncytial virus (RSV) can cause severe disease especially in infants; however, mechanisms of age-associated disease severity remain elusive. Here, employing human bronchial epithelium models generated from tracheal aspirate-derived basal stem cells of neonates and adults, we investigated whether age regulates RSV epithelium interaction to determine disease severity. We show that following RSV infection, only neonatal epithelium model exhibited cytopathy and mucus hyperplasia, and neonatal epithelium had more robust viral spread and inflammatory responses than adult epithelium. Mechanistically, RSV-infected neonatal ciliated cells displayed age-related impairment of STAT3 activation, rendering susceptibility to apoptosis, which facilitated viral spread. In contrast, SARS-CoV-2 infection of ciliated cells had no effect on STAT3 activation and was not affected by age. Taken together, our findings identify an age-related and RSV-specific interaction with neonatal bronchial epithelium that critically contributes to severity of infection, and STAT3 activation offers a potential strategy to battle severe RSV disease in infants.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 56%

Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells

Zhao,

Wang,

Bai

et al. 2023

Preprint

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“…This antagonism of IFN response aids in viral reproduction allowing for further aberrant inflammatory responses, as the IFN response is delayed by about 48 hours 50,51 . Children, however, have a lower threshold to inducing an IFN antiviral response compared to their adult counterparts 51 and upregulated type I and type III IFN‐associated gene expression in tracheobronchial epithelium before infection 52 . This early IFN response in the incubation period of the virus theoretically could limit viral replication in children 51…”

Section: Innate Immune Systemmentioning

confidence: 99%

Insight into the pediatric and adult dichotomy of COVID‐19: Age‐related differences in the immune response to SARS‐CoV‐2 infection

Fialkowski

Gernez

Arya

et al. 2020

Pediatric Pulmonology

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The difference in morbidity and mortality between adult and pediatric coronavirus disease 2019 infections is dramatic. Understanding pediatric‐specific acute and delayed immune responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is critical for the development of vaccination strategies, immune‐targeted therapies, and treatment and prevention of multisystem inflammatory syndrome in children. The goal of this review is to highlight research developments in the understanding of the immune responses to SARS‐CoV‐2 infections, with a specific focus on age‐related immune responses.

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“…Primary human bronchial epithelial cell cultures can show wide interpatient variability in differentiation potential and response to stimulation, and so studying sufficient numbers of patient cultures is crucial, particularly when studying phenomena that are likely to vary with biological characteristics of the donor, such as age and/or sex (Peretz et al, 2016;Maughan et al, 2022). At present, organoid studies typically investigate cells isolated from small numbers of human donors and these cultures are rarely common between investigations from independent laboratories, due to limitations around access to human material, restrictions imposed by ethical approvals, and administrative and practical difficulties in sharing tissue or cultures within and between countries.…”

Section: How Well Do Organoid Cultures Represent Patient Cohorts?mentioning

confidence: 99%

Open questions in human lung organoid research

et al. 2023

Self Cite

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Organoids have become a prominent model system in pulmonary research. The ability to establish organoid cultures directly from patient tissue has expanded the repertoire of physiologically relevant preclinical model systems. In addition to their derivation from adult lung stem/progenitor cells, lung organoids can be derived from fetal tissue or induced pluripotent stem cells to fill a critical gap in modelling pulmonary development in vitro. Recent years have seen important progress in the characterisation and refinement of organoid culture systems. Here, we address several open questions in the field, including how closely organoids recapitulate the tissue of origin, how well organoids recapitulate patient cohorts, and how well organoids capture diversity within a patient. We advocate deeper characterisation of models using single cell technologies, generation of more diverse organoid biobanks and further standardisation of culture media.

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Cell-intrinsic differences between human airway epithelial cells from children and adults

Cited by 10 publications

References 51 publications

Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells

Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells

Insight into the pediatric and adult dichotomy of COVID‐19: Age‐related differences in the immune response to SARS‐CoV‐2 infection

Open questions in human lung organoid research

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