ArticleIn vitro cellular & developmental biology. Animal2026
Serotype-specific effects of adenovirus 5 and 52 E4ORF1 proteins on endothelial cell-mediated regulation of hematopoietic stem cell expansion and lineage differentiation.
Article in In vitro cellular & developmental biology. Animal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Umbilical cord blood HSCs transplantation is limited by low cell numbers and engraftment efficiency. The bone marrow endothelial cell (EC) niche is vital for HSCs. Adenoviral E4ORF1 protein enables ECs (e.g., HUVECs) to support HSCs expansion, but functional differences between E4ORF1 from distinct serotypes (respiratory Ad5 vs. enteric Ad52) are unknown. This study compared Ad5- and Ad52-E4ORF1 effects on engineered HUVECs and their support of hematopoietic stem/progenitor cells (HSPCs). Transcriptome analysis confirmed relevant receptor/metabolism gene expression in HUVECs. Sequence alignment revealed no significant nucleotide/amino acid homology between Ad5- and Ad52-E4ORF1. Engineered HUVECs expressing Ad5- or Ad52-E4ORF1 were co-cultured with mouse HSPCs. Outcomes were assessed via in vitro expansion, flow cytometry phenotyping, and competitive transplantation into irradiated mice evaluating engraftment and multilineage reconstitution. In vitro, Ad5-E4ORF1 promoted greater total hematopoietic cell expansion, while Ad52-E4ORF1 better maintained stemness, yielding a significantly higher proportion of ST-HSCs. Competitive transplantation revealed Ad5-E4ORF1 co-cultured HSPCs achieved higher early engraftment and superior initial myeloid reconstitution. Conversely, Ad52-E4ORF1 supported HSPCs exhibited significantly enhanced and sustained late-phase T-cell production, though B-cell levels declined after 12 weeks. Ad5 and Ad52 E4ORF1 exert serotype-specific regulation on HUVECs, differentially impacting HSPC fate: Ad5-E4ORF1 favors expansion and early myeloid engraftment, while Ad52-E4ORF1 preserves ST-HSCs and enhances short-term T-lymphopoiesis. These differences correlate with high E4ORF1 sequence divergence and are crucial for optimizing HSCs transplantation strategies.
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42240814What Socratic holds
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