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

Morgan Oatley, Özge Vargel Bölükbası, Valentine Svensson, Maya Shvartsman, Kerstin Ganter, Katharina Zirngibl, Polina V. Pavlovich, Vladislava Milchevskaya, Vladimira Foteva, Kedar N. Natarajan, Bianka Baying, Vladimir Benes, Kiran R. Patil, Sarah A. Teichmann, Christophe Lancrin*

*Kontaktforfatter for dette arbejde

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Abstrakt

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.

OriginalsprogEngelsk
Artikelnummer586
TidsskriftNature Communications
Vol/bind11
Udgave nummer1
Antal sider18
ISSN2041-1723
DOI
StatusUdgivet - jan. 2020

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