Effect of AGM and fetal liver-derived stromal cell lines on globin expression in adult baboon (P. anubis) bone marrow-derived erythroid progenitors.
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.
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America. dlavelle@uic.edu
Donald
D
Lavelle
Kestutis
K
Vaitkus
Maria Armila
MA
Ruiz
Vinzon
V
Ibanez
Tatiana
T
Kouznetsova
Yogen
Y
Saunthararajah
Nadim
N
Mahmud
Joseph
J
DeSimone
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000196:embryology; D001854:Bone Marrow Cells / Q000166:cytology*; D002460:Cell Line; D019175:DNA Methylation; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D005333:Fetus / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics*; D006066:Gonads / Q000166:cytology / Q000196:embryology; D008099:Liver / Q000166:cytology*; D008650:Mesonephros / Q000166:cytology / Q000196:embryology; D010215:Papio; D017154:Stromal Cells / Q000166:cytology*
D018952:Antigens, CD34; D005914:Globins