Immature erythroblasts with extensive ex vivo self-renewal capacity emerge from the early mammalian fetus
Immature erythroblasts with extensive ex vivo self-renewal capacity emerge from the early mammalian fetus
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DOI：
10.1182/blood-2010-07-299743
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发表时间：
2011-03-03
期刊：
影响因子：
20.3
通讯作者：
Palis, James
中科院分区：
文献类型：
--
作者：
England, Samantha J.;McGrath, Kathleen E.;Palis, James
在造血层次中，只有干细胞被认为能够长期自我更新。在促红细胞生成素、干细胞因子和地塞米松的存在下，源自胎儿或成年哺乳动物造血组织的红系祖细胞能够进行短期或有限的（10（2）-至10（5）-倍）离体扩增。在这里，我们报告说，初级红系前体来源于早期小鼠胚胎能够广泛（10（6）至10（60）倍）离体增殖。这些细胞在形态学、免疫表型和功能上类似于原成红细胞，尽管培养时间延长，但仍保持细胞因子依赖性和在3 - 4次成熟细胞分裂后产生去核红细胞的潜力。这种广泛的成红细胞自我更新的能力与卵黄囊中确定性红细胞生成的出现及其向胎肝的过渡在时间上相关。相反，成人造血干细胞来源的永久性红细胞生成几乎完全与限制性离体自我更新相关。缺乏Kit和糖皮质激素受体的显著表达的初级原始红细胞前体缺乏离体自我更新能力。广泛自我更新的成红细胞，尽管其在造血系统中接近完全成熟，但最终可作为输血治疗的红细胞的可再生来源。（血。2011; 117（9）：2708 - 2717）
In the hematopoietic hierarchy, only stem cells are thought to be capable of long-term self-renewal. Erythroid progenitors derived from fetal or adult mammalian hematopoietic tissues are capable of short-term, or restricted (10(2)- to 10(5)-fold), ex vivo expansion in the presence of erythropoietin, stem cell factor, and dexamethasone. Here, we report that primary erythroid precursors derived from early mouse embryos are capable of extensive (10(6)- to 10(60)-fold) ex vivo proliferation. These cells morphologically, immunophenotypically, and functionally resemble proerythroblasts, maintaining both cytokine dependence and the potential, despite prolonged culture, to generate enucleated erythrocytes after 3-4 maturational cell divisions. This capacity for extensive erythroblast self-renewal is temporally associated with the emergence of definitive erythropoiesis in the yolk sac and its transition to the fetal liver. In contrast, hematopoietic stem cell-derived definitive erythropoiesis in the adult is associated almost exclusively with restricted ex vivo self-renewal. Primary primitive erythroid precursors, which lack significant expression of Kit and glucocorticoid receptors, lack ex vivo self-renewal capacity. Extensively self-renewing erythroblasts, despite their near complete maturity within the hematopoietic hierarchy, may ultimately serve as a renewable source of red cells for transfusion therapy. (Blood. 2011; 117(9): 2708-2717)