Pulmonary neuroendocrine cells and lung development

Sunday, Mary E.

doi:10.1007/bf02739921

Cited by 29 publications

(14 citation statements)

References 197 publications

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“…Nicotine has been shown to stimulate secretion from PNECs, and smoking increases the number of PNECs (45)(46)(47). PNECs secrete a variety of bioactive compounds, including gastrin-releasing peptide, serotonin, and calcitonin gene-related peptide (70,71), which could all potentially affect lung development. Chromogranin A is present in the secretory granules of PNECs and is an excellent marker of PNECs (49), and, as expected, nicotine modestly increased levels of chromogranin A (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Vitamin C Prevents the Effects of Prenatal Nicotine on Pulmonary Function in Newborn Monkeys

Proskocil

Sekhon

Clark

et al. 2005

Am J Respir Crit Care Med

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Smoking during pregnancy leads to decreased pulmonary function and increased respiratory illness in offspring. Our laboratory has previously demonstrated that many effects of smoking during pregnancy are mediated by nicotine. We now report that vitamin C supplementation can prevent some of the effects of maternal nicotine exposure on pulmonary function of offspring. Timed-pregnant rhesus monkeys were treated with 2 mg/kg/day nicotine bitartrate from Gestation Days 26 to 160. On Gestation Day 160 (term, 165 days) fetuses were delivered by C-section and subjected to pulmonary function testing the following day. Nicotine exposure significantly reduced forced expiratory flows, but supplementation of mothers with 250 mg vitamin C per day prevented the effects of nicotine on expiratory flows. Vitamin C supplementation also prevented the nicotine-induced increases in surfactant apoprotein-B protein. Neither nicotine nor nicotine plus vitamin C significantly affected levels of cortisol or cytokines, which have been shown to affect lung development and surfactant expression. Prenatal nicotine exposure significantly decreased levels of elastin content in the lungs of offspring, and these effects were slightly attenuated by vitamin C. These findings suggest that vitamin C supplementation may potentially be clinically useful to limit the deleterious effects of maternal smoking during pregnancy on offspring's lung function.

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Section: Discussionmentioning

confidence: 99%

Vitamin C Prevents the Effects of Prenatal Nicotine on Pulmonary Function in Newborn Monkeys

Proskocil

Sekhon

Clark

et al. 2005

Am J Respir Crit Care Med

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“…PNEC is signi cantly associated with multiple neurological-related pathways (e.g. sympathetic nervous system development, neuron migration) which supports the neurological sensory function of PNEC 34 . Ciliated cells were associated with GO terms related to positive regulation of transcription from RNA polymerase II promoter and nervous system development, and cycling ciliated cells and ciliated precursors were associated with biological processes related to cell proliferation and transcription-related pathways respectively.…”

Section: Stage-speci C Characterization Of In-vitro Hpsc-derived Fetal Lung Cellsmentioning

confidence: 61%

Modeling lung cell development using human pluripotent stem cells

Wong

2021

Preprint

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Human PSC (hPSC) differentiations can capture developmental phenotypes and processes and are useful for studying fundamental biological mechanisms driving tissue morphogenesis and cell lineage development. Here, we show for the first time the temporal development of lung cell lineages using hPSC that model developmental milestones observed in primary tissue, the generation of renewable fetal lung epithelial spheroids, and the functional utility of the lung models at different differentiation stages for Cystic fibrosis disease modeling. We first show the presence of hPSC-derived lung progenitor cells reminiscent of early trimester lung development and containing basal stem cells that generate renewable airway spheroids. Maturation and polarization in air liquid interface (ALI) generates additional epithelial cell lineages found in adult airways including pulmonary neuroendocrine, brush, mature basal, ciliated and secretory cell types. Finally, pseudotime and RNA velocity analyses of the integrated datasets from the fetal and ALI stages reveal previously identified and new cell lineage relationships. Overall, hPSC differentiation can capture aspects of human lung development and potentially provide important insight into congenital causes of diseases.

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“…The iPNEC differentiation protocol described in this article is adapted from our previously established airway epithelial differentiation protocol to specifically promote differentiation toward the neuroendocrine lineage ). Using this model we are able to generate iPNECs expressing all major PNEC ll OPEN ACCESS iScience Article marker genes including SYP, CHGA, PGP9.5, ROBO2, and ENO2, consistent with primary human and rodent PNECs Linnoila, 2006;Sunday, 1996). By specifically adapting the culture conditions to favor expansion of PNECs we are able to generate cultures with an increased efficiency of generating iPNECs over currently published protocols (Chen et al, 2019).…”

Section: Discussionmentioning

confidence: 94%

Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells

et al. 2020

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Expansion of pulmonary neuroendocrine cells (PNECs) is a pathological feature of many human lung diseases. Human PNECs are inherently difficult to study due to their rarity (<1% of total lung cells) and a lack of established protocols for their isolation. We used induced pluripotent stem cells (iPSCs) to generate induced PNECs (iPNECs), which express core PNEC markers, including ROBO receptors, and secrete major neuropeptides, recapitulating known functions of primary PNECs. Furthermore, we demonstrate that differentiation efficiency is increased in the presence of an air-liquid interface and inhibition of Notch signaling. Single-cell RNA sequencing (scRNA-seq) revealed a PNEC-associated gene expression profile that is concordant between iPNECs and human fetal PNECs. In addition, pseudotime analysis of scRNAseq results suggests a basal cell origin of human iPNECs. In conclusion, our model has the potential to provide an unlimited source of human iPNECs to explore PNEC pathophysiology associated with several lung diseases.

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Pulmonary neuroendocrine cells and lung development

Cited by 29 publications

References 197 publications

Vitamin C Prevents the Effects of Prenatal Nicotine on Pulmonary Function in Newborn Monkeys

Vitamin C Prevents the Effects of Prenatal Nicotine on Pulmonary Function in Newborn Monkeys

Modeling lung cell development using human pluripotent stem cells

Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells

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