Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
PLoS One. 2012;7(5):e36846. doi: 10.1371/journal.pone.0036846. Epub 2012 May 31.
This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction.
在成红细胞分化过程中，红系细胞微环境在调节珠蛋白基因表达方面发挥作用。我们在甲基纤维素、液体培养基中培养成年狨猴骨髓和人脐血 CD34+祖细胞，以及与源自不同发育阶段的基质细胞系在相同支持红系分化的培养基中进行共培养，以研究微环境对珠蛋白基因表达的影响。在液体和甲基纤维素培养基中，成年祖细胞表达高水平的γ-珠蛋白，但在基质细胞共培养中表达低水平的生理γ-珠蛋白。相比之下，γ-珠蛋白在基质细胞系共培养中的脐血祖细胞中仍保持高水平表达。基质细胞系共培养中的成年祖细胞与液体培养基中的γ-珠蛋白基因表达差异需要细胞间接触，并与分化率和γ-珠蛋白启动子 DNA 甲基化的差异相关。我们得出结论，成体来源的红细胞中的 γ-珠蛋白表达可以受到微环境的影响，这提示了 HbF 诱导的新的潜在靶点。
