mNotch1 signaling reduces proliferation of myeloid progenitor cells by altering cell-cycle kinetics

Objective. Notch receptors are involved in the regulation of cell-fate decisions, differentiation, and proliferation in many tissues. The expression of Notch receptors on hemopoietic cells and of cognate ligands on bone marrow stromal cells suggests a possible role for Notch signaling in the regulation of hemopoiesis, me were interested to assess the involvement of Notch1 signaling on cell proliferation of myeloid progenitor cells, Materials and Methods. Proliferation, cell-cycle status, and apoptosis of myeloid progenitor 32D cell lines engineered to permit the conditional induction of the constitutively active intracellular domain of mNotch1 (mN1(IC)) by the 4-hydroxytamoxifen(OHT)-inducible system were analyzed in the presence or absence of OHT. Results. The induction of mN1(IC) by OHT resulted in reduction of proliferation (p < 0.01) and accumulation of cells in the G(1)/G(0) phase of the cell cycle (p < 0.001) without substantially affecting apoptosis of 32D cells, These effects were observed under culture conditions that allow differentiation and, to a lesser degree, under conditions that normally promote self-renewal in the absence of differentiated cells. Conclusion. Our data suggest that mNotch1 signaling suppresses proliferation of myeloid progenitor cells by altering cell-cycle kinetics. (C) 2000 International Society far Experimental Hematology. Published by Elsevier Science Inc.