Leveraging Integrated RNA Sequencing to Decipher Adrenomedullin’s Protective Mechanisms in Experimental Bronchopulmonary Dysplasia

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+/-) 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. This dataset consists of bulk RNA-seq data generated from 12 whole lung tissues ofAdm-haplodeficient(Adm+/-) and WT (Adm+/+) mice in response to LPS (lipopolysaccharide) treatment or control PBS in triplicates.

支气管肺发育不良（Bronchopulmonary dysplasia, BPD）是一类常见累及早产儿的慢性肺部疾病，当前治疗方案有限，且长期不良结局风险显著升高。肾上腺髓质素（Adrenomedullin, Adm）是一种促血管生成肽类激素，既往研究证实其可对实验性BPD啮齿类动物发挥保护作用。本研究拟采用脂多糖（Lipopolysaccharide, LPS）诱导的小鼠实验性BPD模型，阐明Adm调控BPD发病进程的分子与细胞机制。研究对Adm充足型（野生型或Adm+/+）与Adm单倍体缺陷型（Adm+/-）小鼠的肺组织开展批量RNA测序（bulk RNA sequencing），并整合单细胞RNA测序（single-cell RNA sequencing）数据，结果揭示了与Adm缺陷及LPS暴露相关的独特基因表达模式与细胞类型改变。值得注意的是，结合细胞图谱数据的计算整合分析显示，Adm单倍体缺陷型小鼠肺组织呈现出炎症水平升高、自然杀伤（natural killer, NK）细胞频率增加，而内皮细胞与II型肺泡上皮细胞频率降低的基因表达特征。此外，针对人类BPD患者数据的计算机辅助分析验证了上述细胞频率变化结果，提示BPD患儿体内NK细胞水平显著升高。上述结果证实了Adm在实验性BPD中的保护作用，并强调其可作为存在炎症表型的BPD患儿的潜在治疗靶点。本数据集包含针对Adm单倍体缺陷型（Adm+/-）与野生型（Adm+/+）小鼠全肺组织的批量RNA测序数据，这些小鼠分别接受LPS（脂多糖）处理或对照PBS处理，每组均设置3次生物学重复。