{"doi":"10.1101/2024.08.27.609955","title":"Bronchopulmonary Dysplasia with Pulmonary Hypertension Associates with Loss of Semaphorin Signaling and Functional Decrease in FOXF1 Expression","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  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, we performed single-cell RNA sequencing of preterm infant lungs 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\n                  <jats:italic>ANKRD1</jats:italic>\n                  expression. Predictive signaling analysis identified deficits in the semaphorin guidance-cue signaling pathway and decreased expression of pro-angiogenic transcription factor\n                  <jats:italic>FOXF1</jats:italic>\n                  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.\n                </jats:p>","journal":null,"year":null,"id":600935,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":264687,"name":"Nicholas M. Negretti","orcid":"0000-0003-1022-8650","position":1,"is_corresponding":false},{"id":264686,"name":"Christopher S. Jetter","orcid":"0000-0002-3826-5843","position":2,"is_corresponding":false},{"id":1540713,"name":"Alexandria L. Sharkey","orcid":null,"position":3,"is_corresponding":false},{"id":1382134,"name":"Shriya Garg","orcid":null,"position":4,"is_corresponding":false},{"id":1540714,"name":"Meghan E. Kapp","orcid":null,"position":5,"is_corresponding":false},{"id":1540715,"name":"Devan Wilkins","orcid":null,"position":6,"is_corresponding":false},{"id":1540716,"name":"Gabrielle Fortier","orcid":null,"position":7,"is_corresponding":false},{"id":1459048,"name":"Saahithi Mallapragada","orcid":null,"position":8,"is_corresponding":false},{"id":12172,"name":"Nicholas E. Banovich","orcid":"0000-0003-2604-3247","position":9,"is_corresponding":false},{"id":140941,"name":"Christopher V. E. Wright","orcid":null,"position":10,"is_corresponding":false},{"id":260643,"name":"David B. Frank","orcid":"0000-0002-3064-2069","position":11,"is_corresponding":false},{"id":12177,"name":"Jonathan A. Kropski","orcid":"0000-0002-8923-1344","position":12,"is_corresponding":false},{"id":104335,"name":"Jennifer M. S. Sucre","orcid":"0000-0002-6613-1439","position":13,"is_corresponding":false},{"id":1459050,"name":"Shawyon P. Shirazi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Bronchopulmonary Dysplasia with Pulmonary Hypertension Associates with Loss of Semaphorin Signaling and Functional Decrease in FOXF1 Expression","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  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, we performed single-cell RNA sequencing of preterm infant lungs 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\n                  <jats:italic>ANKRD1</jats:italic>\n                  expression. Predictive signaling analysis identified deficits in the semaphorin guidance-cue signaling pathway and decreased expression of pro-angiogenic transcription factor\n                  <jats:italic>FOXF1</jats:italic>\n                  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.\n                </jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39253423","pmcid":null,"openalex_id":"https://openalex.org/W4401936257","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"green","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2024/08/28/2024.08.27.609955.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2024/08/28/2024.08.27.609955.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2024.08.27.609955","host_type":"publisher"},{"url":"https://doi.org/10.1101/2024.08.27.609955","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39253423","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11383282","host_type":"repository"}],"fields_of_study":["Neonatal Respiratory Health Research","Congenital heart defects research","Congenital Diaphragmatic Hernia Studies"],"mesh_terms":[],"keywords":["Bronchopulmonary dysplasia","Semaphorin","Pulmonary hypertension","Medicine","Lung","Respiratory distress","Internal medicine","Cardiology","Immunology","Biology","Receptor","Anesthesia","Genetics","Pregnancy"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T14:36:24.813241Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}