Dual functions of cell-autonomous and non-cell-autonomous ADAM10 activity in granulopoiesis

Masaki Yoda, Tokuhiro Kimura, Takahide Tohmonda, Shinichi Uchikawa, Takeshi Koba, Jiro Takito, Hideo Morioka, Morio Matsumoto, Daniel C. Link, Kazuhiro Chiba, Yasunori Okada, Yoshiaki Toyama, Keisuke Horiuchi

研究成果: Article査読

38 被引用数 (Scopus)


Previous studies have revealed various extrinsic stimuli and factors involved in the regulation of hematopoiesis. Among these, Notch-mediated signaling has been suggested to be critically involved in this process. Herein, we show that conditional inactivation of ADAM10, a membrane-bound protease with a crucial role in Notch signaling (S2 cleavage), results in myeloproliferative disorder (MPD) highlighted by severe splenomegaly and increased populations of myeloid cells and hematopoietic stem cells. Reciprocal transfer of bone marrow cells between wild-type and ADAM10 mutant mice revealed that ADAM10 activity in both hematopoietic and nonhematopoietic cells is involved in the development of MPD. Notably, we found that MPD caused by lack of ADAM10 in nonhematopoietic cells was mediated by G-CSF, whereas MPD caused by ADAM10-deficient hematopoietic cells was not. Taken together, the present findings reveal previously undescribed nonredundant roles of cell-autonomous and non-cell-autonomous ADAM10 activity in the maintenance of hematopoiesis.

出版ステータスPublished - 2011 12月 22

ASJC Scopus subject areas

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学


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