Stephen D. Moore

Research Article| July 01 1998 Taking It like a Man: Masculinity in 4 Maccabees Stephen D. Moore; Stephen D. Moore Search for other works by this author on: This Site Google Janice Capel Anderson Janice Capel Anderson Search for other works by this author on: This Site Google Journal of Biblical Literature (1998) 117 (2): 249–273. https://doi.org/10.2307/3266982 Cite Icon Cite Share Icon Share Facebook Twitter LinkedIn Email Permissions Search Site Citation Stephen D. Moore, Janice Capel Anderson; Taking It like a Man: Masculinity in 4 Maccabees. Journal of Biblical Literature 1 January 1998; 117 (2): 249–273. doi: https://doi.org/10.2307/3266982 Download citation file: Zotero Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All Scholarly Publishing CollectiveSBL PressJournal of Biblical Literature Search Advanced Search The text of this article is only available as a PDF. Article PDF first page preview Close Modal You do not currently have access to this content.

AIMS: Endothelial cell (EC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterize EC dynamics in PAH at single-cell resolution. METHODS AND RESULTS: We carried out single-cell RNA sequencing (scRNA-seq) of lung ECs isolated from an EC lineage-tracing mouse model in Control and SU5416/hypoxia-induced PAH conditions. EC populations corresponding to distinct lung vessel types, including two discrete capillary populations, were identified in both Control and PAH mice. Differential gene expression analysis revealed global PAH-induced EC changes that were confirmed by bulk RNA-seq. This included upregulation of the major histocompatibility complex class II pathway, supporting a role for ECs in the inflammatory response in PAH. We also identified a PAH response specific to the second capillary EC population including upregulation of genes involved in cell death, cell motility, and angiogenesis. Interestingly, four genes with genetic variants associated with PAH were dysregulated in mouse ECs in PAH. To compare relevance across PAH models and species, we performed a detailed analysis of EC heterogeneity and response to PAH in rats and humans through whole-lung PAH scRNA-seq datasets, revealing that 51% of up-regulated mouse genes were also up-regulated in rat or human PAH. We identified promising new candidates to target endothelial dysfunction including CD74, the knockdown of which regulates EC proliferation and barrier integrity in vitro. Finally, with an in silico cell ordering approach, we identified zonation-dependent changes across the arteriovenous axis in mouse PAH and showed upregulation of the Serine/threonine-protein kinase Sgk1 at the junction between the macro- and microvasculature. CONCLUSION: This study uncovers PAH-induced EC transcriptomic changes at a high resolution, revealing novel targets for potential therapeutic candidate development.