A role of EphB4 receptor and its ligand, ephrin-B2, in erythropoiesis.
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.
Suenobu
Souichi
S
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Tokyo, Japan.
Takakura
Nobuyuki
N
Inada
Tomohisa
T
Yamada
Yoshihiro
Y
Yuasa
Hiromi
H
Zhang
Xiu-Qin
XQ
Sakano
Seiji
S
Oike
Yuichi
Y
Suda
Toshio
T
D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D036388:Ephrin-B2; D004920:Erythropoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D017154:Stromal Cells / Q000502:physiology
D036388:Ephrin-B2; D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger