title: Dual functions of cell-autonomous and non-cell-autonomous ADAM10 activity in granulopoiesis.
abstract: 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.
authors: Department of Anti-Aging Orthopedic Research, School of Medicine, Keio University, Tokyo, Japan.
authors: Masaki
authors: M
authors: Yoda
authors: Tokuhiro
authors: T
authors: Kimura
authors: Takahide
authors: T
authors: Tohmonda
authors: Shinichi
authors: S
authors: Uchikawa
authors: Takeshi
authors: T
authors: Koba
authors: Jiro
authors: J
authors: Takito
authors: Hideo
authors: H
authors: Morioka
authors: Morio
authors: M
authors: Matsumoto
authors: Daniel C
authors: DC
authors: Link
authors: Kazuhiro
authors: K
authors: Chiba
authors: Yasunori
authors: Y
authors: Okada
authors: Yoshiaki
authors: Y
authors: Toyama
authors: Keisuke
authors: K
authors: Horiuchi
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000378:metabolism*; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013163:Splenomegaly / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D051881:Receptor, Notch1; D016179:Granulocyte Colony-Stimulating Factor; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse