A role of EphB4 receptor and its ligand, ephrin-B2, in erythropoiesis

Souichi Suenobu, Nobuyuki Takakura, Tomohisa Inada, Yoshihiro Yamada, Hiromi Yuasa, Xiu Qin Zhang, Seiji Sakano, Yuichi Oike, Toshio Suda

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


Erythropoiesis is regulated not only by erythropoietin but also by microenvironments which are composed of transmembrane molecules. We have previously shown that a receptor tyrosine kinase EphB4 is predominantly expressed on human erythroid progenitors in bone marrow. EphB4 is expressed in approximately 45% of hematopoietic progenitor cells, which are CD34-positive and c-Kit-positive in human umbilical cord blood (hUCB). The transmembrane ligand for EphB4 or ephrin-B2 is expressed on bone marrow stromal cells and arterial endothelial cells. When such EphB4-positive hematopoietic progenitor cells were co-cultured with stromal cells which express ephrin-B2, they were immediately detached from stromal cells and differentiated to mature erythroid cells. At that time, expression of EphB4 immediately down-regulated. In contrast, on ephrin-B2 non-expressing stromal cells, they remained EphB4-positive cells and the generated number of mature erythroid cells was less than that on ephrin-B2 expressing stromal cells. Additionally, ephrin-B2 expression on endothelial cells up-regulated under hypoxic condition. Taken together, we propose that one of the molecular cues that regulate erythropoiesis is ephrin-B2 on stromal cells.

Original languageEnglish
Pages (from-to)1124-1131
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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