Prospective isolation of human erythroid lineage-committed progenitors
Prospective isolation of human erythroid lineage-committed progenitors
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DOI：
10.1073/pnas.1512076112
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发表时间：
2015-08-04
影响因子：
11.1
通讯作者：
Weissman, Irving L.
中科院分区：
文献类型：
--
作者：
Mori, Yasuo;Chen, James Y.;Weissman, Irving L.
确定导致红细胞的发育途径并能够分离其祖细胞对于理解和治疗红细胞失衡疾病如贫血、骨髓增生异常综合征和真性红细胞增多症至关重要。在这里，我们表明，人红细胞祖细胞（hEP）可以前瞻性地从成人骨髓中分离。我们发现在先前定义的人巨核细胞/红细胞祖细胞（hMEP;谱系（-）CD 34（+）CD 38（+）IL-3R α（-）CD 45 RA（-））群体中具有不同的CD 105和CD 71表达模式的三个亚组分。至少在体外，CD 71（-）CD 105（-）和CD 71（+）CD 105（-）MEP仍然保留巨核细胞（MegK）和红细胞（E）谱系的双能性，尽管后一亚群在分化上偏向红细胞谱系。值得注意的是，MEP群体中CD 71（intermediate（int）/+）CD 105（+）细胞亚群的增殖和分化输出完全限于红系谱系，并丧失MegK潜能。CD 71 + CD 105-MEP是红细胞偏向的MEP（E-MEP），而CD 71（int/+）CD 105（+）细胞是EP。这些以前未分类的人群可能有助于进一步了解人类红细胞发育的分子机制，并作为红细胞谱系疾病的潜在治疗靶点。
Determining the developmental pathway leading to erythrocytes and being able to isolate their progenitors are crucial to understanding and treating disorders of red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia vera. Here we show that the human erythrocyte progenitor (hEP) can be prospectively isolated from adult bone marrow. We found three subfractions that possessed different expression patterns of CD105 and CD71 within the previously defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage(-) CD34(+) CD38(+) IL-3R alpha(-) CD45RA(-)) population. Both CD71(-) CD105(-) and CD71(+) CD105(-) MEPs, at least in vitro, still retained bipotency for the megakaryocyte (MegK) and erythrocyte (E) lineages, although the latter sub-population is skewed in differentiation toward the erythroid lineage. Notably, the proliferative and differentiation output of the CD71(intermediate(int)/+) CD105(+) subset of cells within the MEP population was completely restricted to the erythroid lineage with the loss of MegK potential. CD71+ CD105- MEPs are erythrocytebiased MEPs (E-MEPs) and CD71(int/+) CD105(+) cells are EPs. These previously unclassified populations may facilitate further understanding of the molecular mechanisms governing human erythroid development and serve as potential therapeutic targets in disorders of the erythroid lineage.