Specification of the haematopoietic stem cell lineage: From blood-fated mesodermal angioblasts to haemogenic endothelium.
Specification of the haematopoietic stem cell lineage: From blood-fated mesodermal angioblasts to haemogenic endothelium.
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DOI：
10.1016/j.semcdb.2022.01.008
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发表时间：
2022-02
影响因子：
7.3
通讯作者：
V. Ho;D. E. Grainger;H. Chagraoui;C. Porcher
中科院分区：
文献类型：
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作者：
V. Ho;D. E. Grainger;H. Chagraoui;C. Porcher
在胚胎发育过程中，造血干和造血祖细胞来自特定血管床中的特化造血内皮细胞。然而，在内皮细胞被赋予造血能力之前，在中胚层构型和产生内皮细胞前体细胞(血管母细胞)的时候，就发生了对血统的指定和承诺。虽然早期血细胞的命运规范早已被认识到，但对诱导内皮细胞多样化和这些细胞亚群逐渐获得血液特性的机制知之甚少。在这里，我们回顾了造血系统的内皮起源和命中注定的血管母细胞的复杂发展历程。我们讨论了最近的技术进步将如何有助于检查胚胎解剖生态位的多样性、信号通路以及控制内皮细胞异质性和血细胞命运规范的下游表观遗传和转录过程。最终，这将给出对产生造血干细胞的细胞个体发育的基本见解，这可能有助于开发用于临床目的的体外生产的新策略。
Haematopoietic stem and progenitor cells emerge from specialized haemogenic endothelial cells in select vascular beds during embryonic development. Specification and commitment to the blood lineage, however, occur before endothelial cells are endowed with haemogenic competence, at the time of mesoderm patterning and production of endothelial cell progenitors (angioblasts). Whilst early blood cell fate specification has long been recognized, very little is known about the mechanisms that induce endothelial cell diversification and progressive acquisition of a blood identity by a subset of these cells. Here, we review the endothelial origin of the haematopoietic system and the complex developmental journey of blood-fated angioblasts. We discuss how recent technological advances will be instrumental to examine the diversity of the embryonic anatomical niches, signaling pathways and downstream epigenetic and transcriptional processes controlling endothelial cell heterogeneity and blood cell fate specification. Ultimately, this will give essential insights into the ontogeny of the cells giving rise to haematopoietic stem cells, that may aid in the development of novel strategies for theirin vitroproduction for clinical purposes.