Revision of the Human Hematopoietic Tree: Granulocyte Subtypes Derive from Distinct Hematopoietic Lineages

Revision of the Human Hematopoietic Tree: Granulocyte Subtypes Derive from Distinct Hematopoietic Lineages
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DOI:
10.1016/j.celrep.2013.04.025
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发表时间:
2013-05-01
期刊:
影响因子:
8.8
通讯作者:
Giebel, Bernd
Giebel, Bernd
中科院分区:
生物学1区
文献类型:
--
作者:
Goergens, Andre;Radtke, Stefan;Giebel, Bernd

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经典的造血模型预测了多能造血祖细胞(MPPs)分为普通淋巴样祖细胞(CLP)和普通髓样祖细胞(CMP)的二分谱系限制。然而,这一想法受到了保留部分骨髓潜能的淋巴祖细胞的鉴定的挑战(例如,LMPPs),这意味着粒细胞可以出现在经典的淋巴和骨髓分支。在这里,我们解决了这个问题,通过使用细胞表面CD133的表达来区分功能祖细胞群体。我们发现,嗜酸性粒细胞和嗜碱性粒细胞以及红细胞和巨核细胞来自一个共同的红骨髓祖细胞(EMP),而嗜酸性粒细胞出现独立的淋巴髓样分支与长期祖细胞功能。这些发现挑战了CMP的概念,并恢复了经典造血模型的二分法。
The classical model of hematopoiesis predicts a dichotomous lineage restriction of multipotent hematopoietic progenitors (MPPs) into common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs). However, this idea has been challenged by the identification of lymphoid progenitors retaining partial myeloid potential (e.g., LMPPs), implying that granulocytes can arise within both the classical lymphoid and the myeloid branches. Here, we resolve this issue by using cell-surface CD133 expression to discriminate functional progenitor populations. We show that eosinophilic and basophilic granulocytes as well as erythrocytes and megakaryocytes derive from a common erythro-myeloid progenitor (EMP), whereas neutrophilic granulocytes arise independently within a lympho-myeloid branch with long-term progenitor function. These findings challenge the concept of a CMP and restore dichotomy to the classical hematopoietic model.