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 and Christophe Lancrin ()
Additional contact information
Morgan Oatley: EMBL Rome - Epigenetics and Neurobiology Unit
Özge Vargel Bölükbası: EMBL Rome - Epigenetics and Neurobiology Unit
Valentine Svensson: Wellcome Trust Sanger Institute
Maya Shvartsman: EMBL Rome - Epigenetics and Neurobiology Unit
Kerstin Ganter: EMBL Rome - Epigenetics and Neurobiology Unit
Katharina Zirngibl: Structural and Computational Biology Unit
Polina V. Pavlovich: EMBL Rome - Epigenetics and Neurobiology Unit
Vladislava Milchevskaya: Structural and Computational Biology Unit
Vladimira Foteva: EMBL Rome - Epigenetics and Neurobiology Unit
Kedar N. Natarajan: Wellcome Trust Sanger Institute
Bianka Baying: Genomics Core Facility
Vladimir Benes: Genomics Core Facility
Kiran R. Patil: Structural and Computational Biology Unit
Sarah A. Teichmann: Wellcome Trust Sanger Institute
Christophe Lancrin: EMBL Rome - Epigenetics and Neurobiology Unit

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-019-14171-5

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