Asymmetrical lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors.
Asymmetrical lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors.
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DOI：
10.1084/jem.20060697
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发表时间：
2006-08-07
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造血干细胞（hsc）的谱系承诺机制尚不清楚。尽管对淋巴或髓系的承诺被普遍认为是造血干细胞谱系限制的第一步，但这种造血分化模型最近受到了挑战。先前鉴定的多能祖细胞（MPPs）可以产生淋巴细胞和粒细胞/巨噬细胞（GMs），但缺乏红细胞分化能力，这表明存在另一种HSC分化程序。然而，这些mpp在生理条件下对不同造血谱系的贡献尚未得到仔细研究。在这项研究中，我们基于Flt3和血管细胞粘附分子1的表达，通过减去三个不同的亚群，对mpp进行了精细的表征。这些MPP亚群产生红系和GM系细胞的能力不同，但在体内淋巴系分化中同样有效。这些MPP亚群的发育层次表明，在早期造血过程中，红细胞和GM分化潜力依次丧失。我们的研究结果表明造血干细胞谱系承继的第一步不仅仅是淋巴和髓系谱系之间的简单选择。
The mechanism of lineage commitment from hematopoietic stem cells (HSCs) is not well understood. Although commitment to either the lymphoid or the myeloid lineage is popularly viewed as the first step of lineage restriction from HSCs, this model of hematopoietic differentiation has recently been challenged. The previous identification of multipotent progenitors (MPPs) that can produce lymphocytes and granulocyte/macrophages (GMs) but lacks erythroid differentiation ability suggests the existence of an alternative HSC differentiation program. Contribution to different hematopoietic lineages by these MPPs under physiological conditions, however, has not been carefully examined. In this study, we performed a refined characterization of MPPs by subfractionating three distinct subsets based on Flt3 and vascular cell adhesion molecule 1 expression. These MPP subsets differ in their ability to give rise to erythroid and GM lineage cells but are equally potent in lymphoid lineage differentiation in vivo. The developmental hierarchy of these MPP subsets demonstrates the sequential loss of erythroid and then GM differentiation potential during early hematopoiesis. Our results suggest that the first step of lineage commitment from HSCs is not simply a selection between the lymphoid and the myeloid lineage.