Identification of two distinct pathways of human myelopoiesis
Identification of two distinct pathways of human myelopoiesis
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DOI：
10.1126/sciimmunol.aau7148
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发表时间：
2019-05-01
影响因子：
24.8
通讯作者：
Nerlov, Claus
中科院分区：
文献类型：
--
作者：
Drissen, Roy;Thongjuea, Supat;Nerlov, Claus
人类骨髓细胞生成被认为是通过寡能共同髓系祖细胞（CMP）和淋巴启动多能祖细胞（LMPP）群体发生的。然而，其他研究提出了多能细胞的直接承诺单系的命运，没有特定的中间谱系共分离模式。我们在这里表明，不同的人骨髓祖细胞群体产生的中性粒细胞/单核细胞和肥大细胞/嗜碱性粒细胞/嗜酸性粒细胞谱系，如先前在小鼠中所示。此外，我们发现，中性粒细胞/单核细胞的潜力选择性cosegregates与淋巴细胞系和肥大细胞/嗜碱性粒细胞/嗜酸性粒细胞的潜力与巨核细胞/红细胞的潜力早期在谱系承诺。此外，在此初始定型步骤后，肥大细胞/嗜碱性粒细胞/嗜酸性粒细胞和巨核细胞/红细胞潜能在限制性寡能祖细胞中以单细胞水平共定位。这些结果表明，人骨髓谱系是通过两种不同的细胞途径产生的，这两种途径由互补的寡能细胞群定义。
Human myelopoiesis has been proposed to occur through oligopotent common myeloid progenitor (CMP) and lymphoid-primed multipotent progenitor (LMPP) populations. However, other studies have proposed direct commitment of multipotent cells to unilineage fates, without specific intermediary lineage cosegregation patterns. We here show that distinct human myeloid progenitor populations generate the neutrophil/monocyte and mast cell/basophil/eosinophil lineages as previously shown in mouse. Moreover, we find that neutrophil/monocyte potential selectively cosegregates with lymphoid lineage and mast cell/basophil/eosinophil potentials with megakaryocyte/erythroid potential early during lineage commitment. Furthermore, after this initial commitment step, mast cell/basophil/eosinophil and megakaryocyte/erythroid potentials colocalize at the single-cell level in restricted oligopotent progenitors. These results show that human myeloid lineages are generated through two distinct cellular pathways defined by complementary oligopotent cell populations.