Bronchopulmonary Dysplasia with Pulmonary Hypertension
Shawyon P. Shirazi1, Nicholas M. Negretti1, Christopher S. Jetter1, Alexandria L. Sharkey1, Shriya Garg1, Meghan E. Kapp2, Devan Wilkins1, Gabrielle Fortier3, Saahithi Mallapragada4, Nicholas E. Banovich4, Christopher V. E. Wright1, David B. Frank5, Jonathan A. Kropski1*, Jennifer M. S. Sucre1*
1Vanderbilt University Medical Center, 2Case Western Reserve University Hospitals, 3Vanderbilt University, 4Translational Genomics Research Institute, 5Children’s Hospital of Philadelphia, *Corresponding author
Description
Lung injury in preterm infants leads to structural and functional respiratory deficits, with a risk for bronchopulmonary dysplasia (BPD) that in its most severe form is accompanied by pulmonary hypertension (PH). To examine cellular and molecular dynamics driving evolving BPD in humans, single-cell RNA sequencing of preterm infant lungs was performed in early stages of BPD and BPD+PH compared to term infants. Analysis of the endothelium revealed a unique aberrant capillary cell-state primarily in BPD+PH marked by ANKRD1 expression. Predictive signaling analysis identified deficits in the semaphorin guidance-cue signaling pathway and decreased expression of pro-angiogenic transcription factor FOXF1 within the alveolar parenchyma in neonatal lung samples with BPD/BPD+PH. Loss of semaphorin signaling was replicated in a murine BPD model and in humans with alveolar capillary dysplasia (ACDMPV), suggesting a mechanistic link between the developmental programs underlying BPD and ACDMPV and a critical role for semaphorin signaling in normal lung development.
LungMAP ID: LMEX0000004401
Organism: human
Stages: neonate | infant
Assay type: Single-cell RNA-seq