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Blood. 2016 Dec 8;128(23):2637-2641. Epub 2016 Oct 24.

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

Author information

1
Whitehead Institute for Biomedical Research, Cambridge, MA.
2
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.
3
Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
4
University of Kansas Medical Center, Kansas City, KS.
5
Institute for Cell Engineering and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD; and.
6
Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA.

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.

PMID:
27777239
PMCID:
PMC5146747
DOI:
10.1182/blood-2016-05-718320
[Indexed for MEDLINE]
Free PMC Article

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