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Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition.

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Oatley, Morgan 
Bölükbası, Özge Vargel  ORCID logo
Svensson, Valentine  ORCID logo
Shvartsman, Maya 
Ganter, Kerstin 


The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening, we identify CD44 as a marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta-gonad-mesonephros (AGM) region. This allows us to provide a detailed phenotypical and transcriptional profile of CD44-positive arterial endothelial cells from which HSPCs emerge. They are characterized with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists, a downregulation of genes related to glycolysis and the TCA cycle, and a lower rate of cell cycle. Moreover, we demonstrate that by inhibiting the interaction between CD44 and its ligand hyaluronan, we can block EHT, identifying an additional regulator of HSPC development.



Animals, Aorta, Arteries, Biomarkers, Cell Cycle, Citric Acid Cycle, Computational Biology, Core Binding Factor Alpha 2 Subunit, Down-Regulation, Endothelium, Glycolysis, Gonads, Hematopoiesis, Hematopoietic Stem Cells, Hyaluronan Receptors, Hyaluronic Acid, Mesonephros, Mice, Mice, Inbred C57BL, Mice, Knockout, Transcriptome, Transforming Growth Factor beta

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Nat Commun

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Springer Science and Business Media LLC