早期造血内皮细胞在单细胞水平上的动态命运变化特征。
Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level.
机构信息
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
出版信息
Nat Commun. 2013;4:2924. doi: 10.1038/ncomms3924.
Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP(+) HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.
造血干细胞（HSCs）是成人造血系统的创始细胞，它们在个体发生过程中从内皮细胞的一个特殊亚群——造血内皮细胞（HE）通过内皮细胞向造血细胞的转变（EHT）产生。尽管最近已经实时成像，但 EHT 的潜在机制仍知之甚少。我们生成了一个 Runx1 +23 增强子报告基因转基因小鼠（23GFP），用于在整个胚胎发育过程中对 HE 的前瞻性分离。在这里，我们对超过 1800 个和 268 个单个 23GFP（+）HE 细胞进行了功能分析和转录分析，以探索单细胞水平上 EHT 的起始。我们表明，造血程序的启动发生在仍嵌入在内皮层中的细胞中，并伴随着 HSCs 出现之前以前未被认识到的内皮潜能的早期丧失。因此，我们的数据为早期造血承诺的时间表提供了重要的见解。
Zotero 插件