Chao Ruihua, Gong Xueping, Wang Libo, Wang Pengxiang, Wang Yuan
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Stem Cell Res. 2015 Jan;14(1):30-8. doi: 10.1016/j.scr.2014.11.002. Epub 2014 Nov 25.
The CD71/Ter119 combination has been widely used to reflect dynamic maturation of erythrocytes in vivo. However, because CD71 is expressed on all proliferating cells, it is unclear whether it can be utilized as an erythrocyte-specific marker during differentiation of embryonic stem cells (ESCs). In this study, we revealed that a population expressing high level of CD71 (CD71(high)) during mouse ESC differentiation represented an in vitro counterpart of yolk sac-derived primitive erythroblasts (EryPs) isolated at 8.5days post coitum. In addition, these CD71(high) cells went through "maturational globin switching" and enucleated during terminal differentiation in vitro that were similar to the yolk sac-derived EryPs in vivo. We further demonstrated that the formation of CD71(high) population was regulated differentially by key factors including Scl, HoxB4, Eaf1, and Klf1. Taken together, our study provides a technical advance that allows efficient segregation of EryPs from differentiated ESCs in vitro for further understanding molecular regulation during primitive erythropoiesis.
CD71/Ter119组合已被广泛用于反映体内红细胞的动态成熟过程。然而,由于CD71在所有增殖细胞上均有表达,因此在胚胎干细胞(ESC)分化过程中,它是否可作为红细胞特异性标志物尚不清楚。在本研究中,我们发现,在小鼠ESC分化过程中,表达高水平CD71(CD71(high))的细胞群代表了在交配后8.5天分离的卵黄囊来源的原始成红细胞(EryP)在体外的对应物。此外,这些CD71(high)细胞在体外终末分化过程中经历了“成熟型珠蛋白转换”并去核,这与体内卵黄囊来源的EryP相似。我们进一步证明,CD71(high)细胞群的形成受到包括Scl、HoxB4、Eaf1和Klf1在内的关键因子的不同调控。综上所述,我们的研究提供了一项技术进展,可在体外从分化的ESC中有效分离EryP,以进一步了解原始红细胞生成过程中的分子调控机制。