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

First Author  Yoda M Year  2011
Journal  Blood Volume  118
Issue  26 Pages  6939-42
PubMed ID  22042698 Mgi Jnum  J:179060
Mgi Id  MGI:5301025 Doi  10.1182/blood-2011-06-357210
Citation  Yoda M, et al. (2011) Dual functions of cell-autonomous and non-cell-autonomous ADAM10 activity in granulopoiesis. Blood 118(26):6939-42
abstractText  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.
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