Project description:During the first days of life, the lung surface area increases explosively to enable efficient oxygen exchange. Alveolarization and angiogenesis involve profound changes within the lung mesenchyme to modulate extracellular matrix composition, tissue elasticity, and coordination with the lung epithelium and endothelium. To define the cell types and states populating the perinatal lung mesenchyme, we performed single cell transcriptomics and in-situ imaging in mice and discovered an extremely heterogeneous and dynamic landscape of fibroblasts, airway smooth muscle-like, and mural cells spanning fourteen distinct populations. In the fibroblast and airway smooth muscle-like compartments, bipotent progenitors differentiate rapidly within one day of birth and then again towards the end of alveolarization, while mural cell types are characterized by slow, gradual changes. Glucocorticoid release, retinoic acid inactivation, and oxygen sensing are controlled by specific stromal progenitors. A population of myofibroblasts arises postnatally, peaks at the onset of alveolarization and disappears before three weeks of age. Paracrine signaling with dozens of lung cell types decreases after birth and especially during alveolarization. Nonetheless, alveolarization is the most proliferative developmental stage, followed by a shift towards cell quiescence. Exposure to hyperoxia during the first week of life delayed the transcriptomic changes of normal development, mirroring the arrested development observed in human neonatal bronchopulmonary dysplasia (BDP). Hyperoxia also caused a severe loss of pericytes and myofibroblasts and reduced their proliferation, decreased mesenchymal-endothelial communications, gave rise to a small novel population of contractile alveolar fibroblasts and increased matrix adhesion and contractility across the mesenchyme.
Project description:During the first days of life, the lung surface area increases explosively to enable efficient oxygen exchange. Perturbations to the neonatal environment can profoundly affect the abundance, gene expression, organisation, and function of lung cells. Here, we build upon previous experiments and exposed newborn mice to 80% oxygen for the first seven days of life, followed by single cell transcriptomics of immune cells.
Project description:We performed miRNA array analysis from 2 groups (neonatal lung control, neonatal lung after hyperoxia). We used pools of every 100ng of total RNA of three samples for each groups.
Project description:Exposure to neonatal hyperoxia is associated with brain injury and poor neurodevelopmental outcomes in preterm infants. Our goal was to determine the pathogenic role of GDMD in hiipocampal in injury in newborn mice
Project description:This experiment aimed to investigate the differences in the transcriptional profile of the neurogenic niche regions of mouse pups that were raised in room air verses mouse pups that were exposed to hyperoxia during the neonatal period. Pups were housed in room air or hyperoxia (85% O2) from P0 to P14. Brain tissue (the subventricular zone and the hippocampus) was collected at P14 and 12 months of age. RNA was extracted from the brain tissue and the microarray labelling, hybridization, and scanning was conducted by the Génome Québec Innovation Centre (Montréal, Canada).
Project description:Bronchopulmonary dysplasia (BPD) is characterized by an arrest in alveolarization, abnormal vascular development and variable interstitial fibroproliferation in the premature lung. Endothelial to mesenchymal transition (Endo-MT) may be a source of pathologic fibrosis in many organ systems. Whether Endo-MT contributes to the pathogenesis of BPD is not known. We tested the hypothesis that pulmonary endothelial cells will show increased expression of Endo-MT markers upon exposure to hyperoxia and that sex as a biological variable will modulate differences in expression. WT and Cdh5-PAC CreERT2 (endothelial reporter) neonatal male and female mice (C57BL6) were exposed to hyperoxia (0.95 FiO2) either during the saccular stage of lung development (95% FiO2; PND1-5) or through the saccular and early alveolar stages of lung development (75% FiO2; PND1-14). Expression of Endo-MT markers were measured in whole lung and endothelial cell mRNA. Sorted lung endothelial cells were subjected to bulk RNA-Seq. We show that exposure of the neonatal lung to hyperoxia leads to upregulation of key markers of EndoMT Neonatal male mice show higher expression of genes related to EndoMT. Furthermore, using lung sc-RNAseq data from neonatal lung we were able to show that xxx. Markers related to Endo-MT are upregulated in the neonatal lung upon exposure to hyperoxia and show sex-specific differences. Mechanisms mediating EndoMT in the injured neonatal lung can modulate the response of the neonatal lung to hyperoxic injury and need further investigation.
Project description:We performed miRNA array analysis from 4 groups (neonatal lung control, neonatal lung after hyperoxia, adult lung control, adult lung after hyperoxia). We used pools of every 100ng of total RNA of three samples for each groups.
Project description:To investigate the role of GSDMD-mediated pyroptosis in neonatal lung and retinal injury induced by hyperoxia We performed RNA-seq of lung and retina of newborn rats exposed to hyperoxia for 2 weeks