Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Curr Opin Hematol. 2020 Jul;27(4):232-240. doi: 10.1097/MOH.0000000000000592.
In hematopoiesis, rapid cell fate decisions are necessary for timely responses to environmental stimuli resulting in the production of diverse types of blood cells. Early studies have led to a hierarchical, tree-like view of hematopoiesis with hematopoietic stem cells residing at the apex and serially branching out to give rise to bipotential progenitors with increasingly restricted lineage potential. Recent single-cell studies have challenged some aspects of the classical model of hematopoiesis. Here, we review the latest articles on cell fate decision in hematopoietic progenitors, highlighting single-cell studies that have questioned previously established concepts and those that have reaffirmed them.
The hierarchical organization of hematopoiesis and the importance of transcription factors have been largely validated at the single-cell level. In contrast, single-cell studies have shown that lineage commitment is progressive rather than switch-like as originally proposed. Furthermore, the reconstruction of cell fate paths suggested the existence of a gradient of hematopoietic progenitors that are in a continuum of changing fate probabilities rather than in a static bipotential state, leading us to reconsider the notion of bipotential progenitors.
Single-cell transcriptomic and proteomic studies have transformed our view of lineage commitment and offer a drastically different perspective on hematopoiesis.
综述目的：在造血过程中，快速的细胞命运决定对于及时响应环境刺激以产生各种类型的血细胞是必要的。早期的研究导致了造血的分层、树状观点，造血干细胞位于顶端，并依次分支，产生具有越来越受限谱系潜能的双潜能祖细胞。最近的单细胞研究挑战了造血经典模型的某些方面。在这里，我们回顾了造血祖细胞中细胞命运决定的最新研究，重点介绍了质疑先前确立的概念和证实这些概念的单细胞研究。
最新发现：造血的层级组织和转录因子的重要性在单细胞水平上得到了很大的验证。相比之下，单细胞研究表明，谱系决定是渐进的，而不是最初提出的开关样的。此外，细胞命运路径的重建表明存在一个造血祖细胞的梯度，这些细胞处于不断变化的命运概率的连续体中，而不是处于静态的双潜能状态，这使我们重新考虑双潜能祖细胞的概念。
总结：单细胞转录组学和蛋白质组学研究改变了我们对谱系决定的看法，为造血提供了截然不同的视角。
