Notch signaling distinguishes 2 waves of definitive hematopoiesis in the zebrafish embryo
Notch signaling distinguishes 2 waves of definitive hematopoiesis in the zebrafish embryo
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DOI：
10.1182/blood-2009-09-244590
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发表时间：
2010-04-08
期刊：
影响因子：
20.3
通讯作者：
Traver, David
中科院分区：
文献类型：
--
作者：
Bertrand, Julien Y.;Cisson, Jennifer L.;Traver, David
最近的研究表明，脊椎动物的最终造血始于一种非自我更新的祖细胞的形成，这种祖细胞具有有限的多系分化潜力，称为红髓祖细胞（EMP）。emp是在造血干细胞（hsc）之前被指定的，造血干细胞自我更新并能够形成包括淋巴样细胞在内的所有成熟成人血液谱系。尽管存在差异，但emp和hsc具有许多共同的表型特征，这使得对其各自功能的精确研究变得困难。在这里，我们研究胚胎emp的形成是否需要Notch信号，正如造血干细胞所显示的那样。在缺乏功能性Notch配体的心智炸弹突变体中，我们发现EMPs被正常指定：我们发现从野生型（WT）或心智炸弹突变胚胎中纯化的EMPs在细胞数量、基因表达或分化能力方面没有显著差异。同样，N-[N-（3,5-二氟苯乙酰基）- l -丙氨基]s -苯基甘氨酸t-丁基酯（DAPT）是Notch受体激活的化学抑制剂，对EMP规范没有影响。这些研究证实造血干细胞是唯一需要Notch信号的造血前体，并有助于阐明确定造血的两种不同波的信号事件。（Blood. 2010; 115(14): 2777-2783）
Recent studies have revealed that definitive hematopoiesis in vertebrates initiates through the formation of a non-self-renewing progenitor with limited multi-lineage differentiation potential termed the erythromyeloid progenitor (EMP). EMPs are specified before hematopoietic stem cells (HSCs), which self-renew and are capable of forming all mature adult blood lineages including lymphoid cells. Despite their differences, EMPs and HSCs share many phenotypic traits, making precise study of their respective functions difficult. Here, we examine whether embryonic specification of EMPs requires Notch signaling as has been shown for HSCs. In mindbomb mutants, which lack functional Notch ligands, we show that EMPs are specified normally: we detect no significant differences in cell number, gene expression, or differentiation capacity between EMPs purified from wildtype (WT) or mindbomb mutant embryos. Similarly N-[N-(3,5-difluorophenacetyl)-L-alanyl]S-phenylglycine t-butyl ester (DAPT), a chemical inhibitor of Notch receptor activation, has no effect on EMP specification. These studies establish that HSCs are the only hematopoietic precursor that requires Notch signaling and help to clarify the signaling events underlying the specification of the 2 distinct waves of definitive hematopoiesis. (Blood. 2010; 115(14): 2777-2783)