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

First Author  Oatley M Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  586
PubMed ID  31996681 Mgi Jnum  J:283884
Mgi Id  MGI:6387874 Doi  10.1038/s41467-019-14171-5
Citation  Oatley M, et al. (2020) Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition. Nat Commun 11(1):586
abstractText  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.
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