TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors

X Gao, HY Lee, EL Da Rocha, C Zhang… - Blood, The Journal …, 2016 - ashpublications.org
X Gao, HY Lee, EL Da Rocha, C Zhang, YF Lu, D Li, Y Feng, J Ezike, RR Elmes, MI Barrasa…
Blood, The Journal of the American Society of Hematology, 2016ashpublications.org
Burst-forming unit erythroid progenitors (BFU-Es) are so named based on their ability to
generate in methylcellulose culture large colonies of erythroid cells that consist of “bursts” of
smaller erythroid colonies derived from the later colony-forming unit erythroid progenitor
erythropoietin (Epo)–dependent progenitors.“Early” BFU-E cells forming large BFU-E
colonies presumably have higher capacities for self-renewal than do “late” BFU-Es forming
small colonies, but the mechanism underlying this heterogeneity remains unknown. We …
Abstract
Burst-forming unit erythroid progenitors (BFU-Es) are so named based on their ability to generate in methylcellulose culture large colonies of erythroid cells that consist of “bursts” of smaller erythroid colonies derived from the later colony-forming unit erythroid progenitor erythropoietin (Epo)–dependent progenitors. “Early” BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do “late” BFU-Es forming small colonies, but the mechanism underlying this heterogeneity remains unknown. We show that the type III transforming growth factor β (TGF-β) receptor (TβRIII) is a marker that distinguishes early and late BFU-Es. Transient elevation of TβRIII expression promotes TGF-β signaling during the early BFU-E to late BFU-E transition. Blocking TGF-β signaling using a receptor kinase inhibitor increases early BFU-E cell self-renewal and total erythroblast production, suggesting the usefulness of this type of drug in treating Epo-unresponsive anemias.
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