Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition
Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition
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DOI：
10.1038/s41467-019-14171-5
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发表时间：
2020-01-29
影响因子：
16.6
通讯作者：
Lancrin, Christophe
中科院分区：
文献类型：
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作者：
Oatley, Morgan;Bolukbasi, Ozge Vargel;Lancrin, Christophe
内皮细胞向造血细胞转化（EHT）是造血内皮细胞分化为造血干细胞和祖细胞（HSPC）的过程。该过程的中间步骤尚不清楚，特别是产生HSPC的内皮细胞的身份尚不清楚。使用单细胞转录组分析和抗体筛选，我们确定CD 44作为EHT的标志物，使我们能够在性腺-中肾（AGM）区域分离出EHT的不同阶段。这使我们能够提供CD 44阳性动脉内皮细胞的详细表型和转录谱，HSPC从中出现。其特征在于与Notch信号传导、TGF β/BMP拮抗剂相关的基因的高表达，与糖酵解和TCA循环相关的基因的下调，以及较低的细胞周期速率。此外，我们证明，通过抑制CD 44及其配体透明质酸之间的相互作用，我们可以阻断EHT，确定HSPC发展的额外调节因子。
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.