title: TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors.
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.
authors: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors: Xiaofei
authors: 0000-0003-2799-7421
authors: X
authors: Gao
authors: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors: Hsiang-Ying
authors: 0000-0002-1503-5818
authors: HY
authors: Lee
authors: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.
authors: Edroaldo Lummertz
authors: EL
authors: da Rocha
authors: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.
authors: Cheng
authors: C
authors: Zhang
authors: Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
authors: Yi-Fen
authors: YF
authors: Lu
authors: University of Kansas Medical Center, Kansas City, KS.
authors: Dandan
authors: D
authors: Li
authors: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors: Yuxiong
authors: Y
authors: Feng
authors: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors: Jideofor
authors: J
authors: Ezike
authors: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors: Russell R
authors: RR
authors: Elmes
authors: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors: M Inmaculada
authors: MI
authors: Barrasa
authors: Institute for Cell Engineering and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD; and.
authors: Patrick
authors: P
authors: Cahan
authors: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.
authors: Hu
authors: H
authors: Li
authors: Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
authors: George Q
authors: GQ
authors: Daley
authors: Whitehead Institute for Biomedical Research, Cambridge, MA.|Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA.
authors: Harvey F
authors: HF
authors: Lodish
mesh_terms: D000740:Anemia / Q000378:metabolism / Q000628:therapy; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism; D006801:Humans; D051379:Mice; D011509:Proteoglycans / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D004921:Erythropoietin; C071736:betaglycan