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

Blood. 2016 Dec 8;128(23):2637-2641. doi: 10.1182/blood-2016-05-718320. Epub 2016 Oct 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / metabolism
  • Anemia / therapy
  • Animals
  • Antigens, Differentiation / metabolism*
  • Erythrocytes / cytology
  • Erythrocytes / metabolism*
  • Erythroid Precursor Cells / cytology
  • Erythroid Precursor Cells / metabolism*
  • Erythropoietin / metabolism
  • Humans
  • Mice
  • Proteoglycans / metabolism*
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / metabolism*


  • Antigens, Differentiation
  • Proteoglycans
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Erythropoietin
  • betaglycan