Image-based spatial transcriptomics analysis of epithelial cell types in acute neonatal lung injury
Alveologenesis is the process of alveolar development in the lung tissue, occurring between 16 weeks of gestational age to 21 years. The structure of the alveoli is supported by the epithelium, which forms a layer between the airspace and lung tissue. We investigated epithelial cell types to study acute neonatal lung injury, which results in arrested alveologenesis and alveolar dysregulation. It affects predominantly premature babies, particularly those born before 26 weeks. The cause of the condition is unknown, but it has been characterized to develop with environmental factors, such as respiratory trauma. We analyzed 17 pediatric lung samples, that were categorized into 5 phenotypes. We analyzed these samples with the 10X Genomics Xenium platform to obtain spatial transcriptomic data, which provides information about gene transcripts’ localization and placement in the tissue. This data supplied the gene expression patterns of the cells in the samples. We ran an algorithm on the data to cluster cells together based on similarity in gene expression. Thereafter, we subset all the clusters that expressed EPCAM, the canonical marker gene for epithelial cells, for cell type annotation. We performed propeller analysis to find significant differences in cell abundance between the premature injured and uninjured samples. 10 cell types had significant differences in proportions between the groups. In the future, we plan to determine the differential expression in all cell lineages to characterize the molecular profile within acute neonatal lung injury.
