Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0380, USA.
Blood. 2010 Apr 8;115(14):2777-83. doi: 10.1182/blood-2009-09-244590. Epub 2010 Jan 27.
Recent studies have revealed that definitive hematopoiesis in vertebrates initiates through the formation of a non-self-renewing progenitor with limited multilineage 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 wild-type (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.
最近的研究表明，脊椎动物中明确的造血作用是通过形成一种非自我更新的祖细胞开始的，这种祖细胞具有有限的多谱系分化潜能，称为红骨髓-髓系祖细胞（EMP）。EMP 在造血干细胞（HSCs）之前被指定，HSCs 自我更新并能够形成包括淋巴细胞在内的所有成熟的成人血液谱系。尽管它们有差异，但 EMP 和 HSCs 具有许多表型特征，这使得精确研究它们各自的功能变得困难。在这里，我们研究了 EMP 的胚胎特异性是否需要 Notch 信号，就像已经证明的 HSCs 一样。在缺乏功能性 Notch 配体的 mindbomb 突变体中，我们表明 EMP 被正常指定：我们没有检测到从野生型（WT）或 mindbomb 突变体胚胎中纯化的 EMP 在细胞数量、基因表达或分化能力方面有显著差异。同样，N-[N-(3,5-二氟苯乙酰基)-l-丙氨酰]-S-苯甘氨酸叔丁酯（DAPT），一种 Notch 受体激活的化学抑制剂，对 EMP 特异性没有影响。这些研究确立了 HSCs 是唯一需要 Notch 信号的造血前体细胞，并有助于阐明明确的造血作用的 2 个不同波次的特异性背后的信号事件。
