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Effect of AGM and Fetal Liver-Derived Stromal Cell Lines on Globin Expression in Adult Baboon (P. anubis) Bone Marrow-Derived Erythroid Progenitors

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posted on 12.11.2013 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 microenvironment on globin gene expression. Adult progenitors express high levels of c-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, c-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in c-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 c-globin promoter DNA methylation. We conclude that c-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction.

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This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) (U54HL090513) and State of Illinois Sickle Cell Center funds

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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. The original version is available through Public Library of Science at DOI: 10.1371/journal.pone.0036846

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Public Library of Science

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en_US

issn

1932-6203

Issue date

01/05/2012

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