4.7 Article

CD82 expression marks the endothelium to hematopoietic transition at the onset of blood specification in human

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ISCIENCE
卷 26, 期 9, 页码 -

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CELL PRESS
DOI: 10.1016/j.isci.2023.107583

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During embryonic development, blood progenitors are derived from endothelial cells via an endothelial-to-hematopoietic transition. However, little is known about the molecular characteristics of the hemogenic endothelium and the molecular changes during this transition. In this study, we analyzed a population of human embryonic stem cell-derived endothelial cells and found that endothelial cells expressing RUNX1 exhibit enriched hemogenic potential and minimal molecular differences compared to their endothelial counterparts. Additionally, we identified CD82 as a marker of the endothelium-to-hematopoietic transition.
During embryonic development, all blood progenitors are initially generated from endothelial cells that acquire a hemogenic potential. Blood progenitors emerge through an endothelial-to-hematopoietic transition regulated by the transcription factor RUNX1. To date, we still know very little about the molecular characteristics of hemogenic endothelium and the molecular changes underlying the transition from endothelium to hematopoiesis. Here, we analyzed at the single cell level a human embryonic stem cell-derived endothelial population containing hemogenic potential. RUNX1-expressing endothelial cells, which harbor enriched hemogenic potential, show very little molecular differences to their endothelial counterpart suggesting priming toward hemogenic potential rather than commitment. Additionally, we identify CD82 as a marker of the endothelium-to-hematopoietic transition. CD82 expression is rapidly upregulated in newly specified blood progenitors then rapidly downregulated as further differentiation occurs. Together our data suggest that endothelial cells are first primed toward hematopoietic fate, and then rapidly undergo the transition from endothelium to blood.

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