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

Research output: Contribution to journalArticlepeer-review

39 Citations (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.

Original languageEnglish
Pages (from-to)6939-6942
Number of pages4
Issue number26
Publication statusPublished - 2011 Dec 22

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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