{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:12:22Z","timestamp":1760145142693,"version":"build-2065373602"},"reference-count":118,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institutes of Science Grant","award":["R01HL139594","1S10OD023469"],"award-info":[{"award-number":["R01HL139594","1S10OD023469"]}]},{"name":"the Genomic and RNA Profiling Core at Baylor College of Medicine with funding","award":["R01HL139594","1S10OD023469"],"award-info":[{"award-number":["R01HL139594","1S10OD023469"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm+\/+) and Adm-haplodeficient (Adm+\/\u2212) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency and LPS exposure. Notably, computational integration with cell atlas data revealed that Adm-haplodeficient mouse lungs exhibited gene expression signatures characteristic of increased inflammation, natural killer (NK) cell frequency, and decreased endothelial cell and type II pneumocyte frequency. Furthermore, in silico human BPD patient data analysis supported our cell type frequency finding, highlighting elevated NK cells in BPD infants. These results underscore the protective role of Adm in experimental BPD and emphasize that it is a potential therapeutic target for BPD infants with an inflammatory phenotype.<\/jats:p>","DOI":"10.3390\/genes15060806","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T05:27:19Z","timestamp":1718861239000},"page":"806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Leveraging Integrated RNA Sequencing to Decipher Adrenomedullin\u2019s Protective Mechanisms in Experimental Bronchopulmonary Dysplasia"],"prefix":"10.3390","volume":"15","author":[{"given":"Subarna","family":"Palit","sequence":"first","affiliation":[{"name":"TUM School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amrit Kumar","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-1900","authenticated-orcid":false,"given":"Shyam","family":"Thapa","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0682-3134","authenticated-orcid":false,"given":"Sandra","family":"L. Grimm","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian","family":"Coarfa","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Theis","sequence":"additional","affiliation":[{"name":"TUM School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany"},{"name":"Institute of Computational Biology, Helmholtz Zentrum M\u00fcnchen, 85764 Neuherberg, Germany"},{"name":"Department of Mathematics, Technical University of Munich, 85748 Garching, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6148-8861","authenticated-orcid":false,"given":"Lukas M.","family":"Simon","sequence":"additional","affiliation":[{"name":"Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8119-5783","authenticated-orcid":false,"given":"Binoy","family":"Shivanna","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151638","DOI":"10.1016\/j.semperi.2022.151638","article-title":"Contributions of the NICHD neonatal research network to the diagnosis, prevention, and treatment of bronchopulmonary dysplasia","volume":"46","author":"Jensen","year":"2022","journal-title":"Semin. 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