Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition.
Morgan OatleyÖzge Vargel BölükbasıValentine SvenssonMaya ShvartsmanKerstin GanterKatharina ZirngiblPolina V PavlovichVladislava MilchevskayaVladimira FotevaKedar Nath NatrajanBianka BayingVladimir BenesKiran Raosaheb PatilSarah A TeichmannChristophe LancrinPublished in: Nature communications (2020)
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.
Keyphrases
- single cell
- endothelial cells
- cell cycle
- cell proliferation
- genome wide
- rna seq
- transcription factor
- nk cells
- high throughput
- poor prognosis
- signaling pathway
- gene expression
- mesenchymal stem cells
- dna methylation
- oxidative stress
- vascular endothelial growth factor
- pulmonary artery
- genome wide identification
- high glucose