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
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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.
Dataset ID LMEX0000004401
Assay Type Single-cell RNA-seq
Organism Human
Stages Neonate | Infant
Cell Count 43607
Technology 10x Genomics Chromium Single Cell Gene Expression
Reference Shirazi, et al. (2024)
FileDescriptionSize
BPD_VUMC_release.h5adRelease object for this study, HDF5 AnnData with gzip compression inside the file, so it opens directly. 43,607 cells x 36,601 genes over 33 author cell types and 7 donors. X is the AUTHORS' own matrix, the natural log of one plus counts per ten thousand; the site viewers read the same values divided by ln(2). obs carries the cell type, its lineage, the donor, the condition, sex and age.222.7 MB
LungMAP IDAlt IDSpeciesSexAgeAge GroupHealth Status
LMSPBPD0000001Acute preterm injury 1Homo sapiensMale26 weeksInfantAcute preterm injury
LMSPBPD0000002BPD 1Homo sapiensFemale7 monthsInfantBPD
LMSPBPD0000003BPD 2Homo sapiensFemale7 monthsInfantBPD
LMSPBPD0000004BPD+PH 1Homo sapiensFemale7 monthsInfantBPD+PH
LMSPBPD0000005BPD+PH 2Homo sapiensFemale7 monthsInfantBPD+PH
LMSPBPD0000006Term infant 1Homo sapiensMale0 daysInfantTerm infant
LMSPBPD0000007Term infant 2Homo sapiensFemale20 daysInfantTerm infant