Souichi Suenobu

Publications (3)7.45 Total impact

• Article: Cell adhesion to ephrinb2 is induced by EphB4 independently of its kinase activity.

  Hiroshi Sakamoto, Xiu-Qin Zhang, Souichi Suenobu, Kazuyuki Ohbo, Minetaro Ogawa, Toshio Suda
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  ABSTRACT: Cell to cell interaction in bone marrow is crucial for differentiation of hematopoietic cells. We have shown that EphB4 receptor is expressed in erythroid progenitor and its activation accelerates erythroid differentiation. To elucidate the role of EphB4 activation in erythropoiesis, we analyzed effects of EphB4 on cell adhesive pathways. Cell adhesion with the extension of filopodial pseudopod was observed by EphB4 activation. EphB4 activation also enhanced an effect of fibronectin-mediated adhesive pathway along with formation of the c-Cbl/CrkL complex. The tyrosine kinase activity of EphB4 was dispensable for those phenomena. These results suggest that activation of EphB4 participates in adhesive but not repulsive signals independently of its tyrosine kinase activity in hematopoietic cells.
  Biochemical and Biophysical Research Communications 09/2004; 321(3):681-7. · 2.48 Impact Factor
• Source

  Available from: Hitomi Nagayama

  Article: Analysis of human TIE2 function on hematopoietic stem cells in umbilical cord blood.

  Hiromi Yuasa, Nobuyuki Takakura, Taizou Shimomura, Souichi Suenobu, Taketo Yamada, Hitomi Nagayama, Yuichi Oike, Toshio Suda
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  ABSTRACT: To investigate the behavior of hematopoietic stem cells (HSCs) in cord blood (CB), we analyzed the expression and function of TIE2, a tyrosine kinase receptor. A subpopulation of Lineage (Lin)(-/low)CD34(+) cells in CB expressed TIE2 (18.8%). Assays for long-term culture-initiating cells (LTC-IC) and cobble-stone formation revealed that Lin(-/low)CD34(+)TIE2(+) cells showed to have a capacity of primitive hematopoietic precursor cells in vitro. When Lin(-/low)CD34(+)TIE2(+) cells were cultured on the stromal cells, they transmigrated under the stromal layers and kept an immature character for a few weeks. By contrast, Lin(-/low)CD34(+)TIE2(-) cells differentiated immediately within a few weeks. Finally, we confirmed that 1x10(4)Lin(-/low)CD34(+)TIE2(+) cells were engrafted in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, while 1x10(4)Lin(-/low)CD34(+)TIE2(-) cells were not. Taken together, we conclude that TIE2 is a marker of HSCs in CB. A ligand for TIE2, Ang-1 promoted the adhesion of sorted primary Lin(-/low)CD34(+)TIE2(+) cells to fibronectin (FN), and this adhesion may play a critical role in keeping HSCs in an immature status under the stromal cells.
  Biochemical and Biophysical Research Communications 12/2002; 298(5):731-7. · 2.48 Impact Factor
• Source

  Available from: Yuichi Oike

  Article: 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
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  ABSTRACT: 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.
  Biochemical and Biophysical Research Communications 06/2002; 293(3):1124-31. · 2.48 Impact Factor