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

Xiaofei Gao, Hsiang Ying Lee, Edroaldo Lummertz Da Rocha, Cheng Zhang, Yi Fen Lu, Dandan Li, Yuxiong Feng, Jideofor Ezike, Russell R. Elmes, M. Inmaculada Barrasa, Patrick Cahan, Hu Li, George Q. Daley, Harvey F. Lodish

Research output: Contribution to journalArticle

18 Scopus citations

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 b (TGF-b) receptor (TbRIII) is a marker that distinguishes early and late BFU-Es. Transient elevation of TbRIII expression promotes TGF-b signaling during the early BFU-E to late BFU-E transition. Blocking TGF-b 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.

Original languageEnglish (US)
Pages (from-to)2637-2641
Number of pages5
JournalBlood
Volume128
Issue number23
DOIs
StatePublished - Dec 8 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Gao, X., Lee, H. Y., Da Rocha, E. L., Zhang, C., Lu, Y. F., Li, D., Feng, Y., Ezike, J., Elmes, R. R., Inmaculada Barrasa, M., Cahan, P., Li, H., Daley, G. Q., & Lodish, H. F. (2016). TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors. Blood, 128(23), 2637-2641. https://doi.org/10.1182/blood-2016-05-718320