Definitive-like etythroid cells derived from human embryonic stem cells coexpress high levels of embryonic and fetal globins with little or no adult globin
Definitive-like etythroid cells derived from human embryonic stem cells coexpress high levels of embryonic and fetal globins with little or no adult globin
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DOI：
10.1182/blood-2005-11-011874
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发表时间：
2006-09-01
期刊：
影响因子：
20.3
通讯作者：
Papayannopoulou, Thalia
中科院分区：
文献类型：
--
作者：
Chang, Kai-Hsin;Nelson, Angelique M.;Papayannopoulou, Thalia
人类胚胎干细胞是一种很有前途的工具，可以用来研究与最早的个体发育阶段的造血相关的事件。我们描述了从HES(H1)通过随后的处理产生红系细胞的过程，这些细胞存在于类胚体分化的早期和晚期。造血标记物的出现动力学表明，CD45(+)造血在D14EB分化晚期达到高峰，尽管在此阶段之前可以看到低水平的CD45(-)红系分化。根据形态标准，HES来源的红系细胞是明确的类型，但这些细胞在mRNA和蛋白质水平上共同表达高水平的胚胎(Epsilon)和胎儿(Gamma)珠蛋白，很少或没有成体珠蛋白(β)。在红系分化过程中，这种珠蛋白表达模式不受胎牛血清、血管内皮生长因子、Flt3-L或与Op-9共培养的影响，也不依赖于培养时间。明确类型的红系细胞同时表达胚胎和胎儿珠蛋白并不能忠实地模仿卵黄囊胚胎或它们的胚胎肝脏。然而，从胚胎干细胞产生的红系细胞共表达胚胎和胎儿珠蛋白的频率很高，这可以作为进一步探索分子机制的宝贵工具。
Human embryonic stem cells are a promising tool to study events associated with the earliest ontogenetic stages of hematopoiesis. We describe the generation of erythroid cells from hES (H1) by subsequent processing of cells present at early and late stages of embryoid body (EB) differentiation. Kinetics of hematopoietic marker emergence suggest that CD45(+) hematopoiesis peaks at late D14EB differentiation stages, although low-level CD45(-) erythroid differentiation can be seen before that stage. By morphologic criteria, hES-derived erythroid cells were of definitive type, but these cells both at mRNA and protein levels coexpressed high levels of embryonic (epsilon) and fetal (gamma) globins, with little or no adult globin (beta). This globin expression pattern was not altered by the presence or absence of fetal bovine serum, vascular endothelial growth factor, Flt3-L, or coculture with Op-9 during erythroid differentiation and was not culture time dependent. The coexpression of both embryonic and fetal globins by definitive-type erythroid cells does not faithfully mimic either yolk sac embryonic or their fetal liver counterparts. Nevertheless, the high frequency of erythroid cells coexpressing embryonic and fetal globin generated from embryonic stem cells can serve as an invaluable tool to further explore molecular mechanisms.