| Autor: |
Sheng Xia, Lisandra Vila Ellis, Konner Winkley, Heather Menden, Sherry M. Mabry, Daniel Louiselle, Margaret Gibson, Elin Grundberg, Jichao Chen, Venkatesh Sampath |
| Rok vydání: |
2022 |
| Popis: |
Hyperoxia (HOX) disrupts lung development in mice and causes bronchopulmonary dysplasia (BPD) in neonates. To investigate sex-dependent molecular and cellular programming involved in HOX, we surveyed the mouse lung using single cell RNA sequencing (scRNA-seq), and validated our findings in human neonatal lung cells in vitro. HOX-induced inflammation in alveolar type (AT) 2 cells gave rise to damage associated transient progenitors (DATP). It also induced a new subpopulation of AT1 cells with reduced expression of growth factors normally secreted by AT1 cells, but increased mitochondrial gene expression. Female alveolar epithelial cells had less EMT and pulmonary fibrosis signaling in HOX. In the endothelium, expansion of Car4+ EC (Cap2) was seen in HOX along with an emergent subpopulation of Cap2 with repressed VEGF signaling. This regenerative response was increased in females exposed to HOX. Mesenchymal cells had inflammatory signatures in HOX, with a new distal interstitial fibroblast subcluster characterized by repressed lipid biosynthesis and a transcriptomic signature resembling myofibroblasts. HOX-induced gene expression signatures in human neonatal fibroblasts and alveolar epithelial cells in vitro resembled mouse scRNA-seq data. These findings suggest that neonatal exposure to HOX programs distinct sex-specific stem cell progenitor and cellular reparative responses that underpin lung remodeling in BPD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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