RT Journal Article
SR Electronic
T1 Single cell RNA analysis of cellular niche in normal and impaired late lung development
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 5242
DO 10.1183/13993003.congress-2020.5242
VO 56
IS suppl 64
A1 Ivana Mizikova
A1 Maria Hurskainen
A1 David Cook
A1 Chanéle Cyr-Depauw
A1 Flore Lesage
A1 Noora Andresson
A1 Emmi Helle
A1 Laurent Renesme
A1 Robert Jankov
A1 Markku Heikinheimo
A1 Barbara Vanderhyden
A1 Bernard Thèbaud
YR 2020
UL http://erj.ersjournals.com/content/56/suppl_64/5242.abstract
AB The chronic lung disease bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants. It is characterized by alveolar hypoplasia and dysmorphic vasculature. Changes in cellular composition and gene expression underlying the development of BPD are not fully understood. Here we created a detailed temporal map of normal and aberrant late lung development using single-cell RNA sequencing on lung cells from 36 mice at postnatal days (P) 3, 7 and 14. BPD was mimicked by exposure to hyperoxia (85% O2). The MULTI-seq labeling was used in order to minimize experimental bias and increase the reproducibility. A total of 66.200 cells were analyzed throughout three crucial time points of late lung development, across which we identified 1 mesothelial, 5 epithelial, 6 stromal, 5 endothelial, 8 myeloid and 9 lymphoid cell clusters. All cell compartments followed developmental trajectories and hyperoxic exposure impaired the composition and expression patterns in all compartments. Specifically, hyperoxia impaired epithelial surfactant homeostasis and halted fibroblasts maturation. The number of capillary endothelial cells was significantly reduced, suggesting that hyperoxia impairs endothelial maturation at a critical stage of capillary development. Hyperoxia altered lung macrophage populations by reducing the number of homeostatic alveolar macrophages and diminishing the proliferating macrophages. Additionally, we identified the effector cells of the innate immune response, thought to orchestrate pivotal processes resulting in lung impairment. Understanding the temporal changes on transcriptional level provides new means to study the pathogenesis and novel therapies for BPD.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 5242.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).