journal.pone.0036846.pdf (1.58 MB)
Effect of AGM and Fetal Liver-Derived Stromal Cell Lines on Globin Expression in Adult Baboon (P. anubis) Bone Marrow-Derived Erythroid Progenitors
journal contribution
posted on 2013-11-12, 00:00 authored by Donald Lavelle, Kestutis Vaitkus, Maria Armila Ruiz, Vinzon Ibanez, Tatiana Kouznetsova, Yogen Saunthararajah, Nadim Mahmud, Joseph DeSimoneThis 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.
Funding
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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Publisher Statement
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.0036846Publisher
Public Library of ScienceLanguage
- en_US
issn
1932-6203Issue date
2012-05-01Usage metrics
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