by Donald Lavelle, Kestutis Vaitkus, Maria Armila Ruiz, Vinzon Ibanez, Tatiana Kouznetsova, Yogen Saunthararajah, Nadim Mahmud, Joseph DeSimone
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 ?-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, ?-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in ?-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 ?-globin promoter DNA methylation. We conclude that ?-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction.