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

Objective. Notch receptors are involved in the regulation of cell-fate deci sions, differentiation, and proliferation in many tissues. The expression o f Notch receptors on hemopoietic cells and of cognate ligands on bone marro w stromal cells suggests a possible role for Notch signaling in the regulat ion 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 m yeloid progenitor 32D cell lines engineered to permit the conditional induc tion of the constitutively active intracellular domain of mNotch1 (mN1(IC)) by the 4-hydroxytamoxifen(OHT)-inducible system were analyzed in the prese nce or absence of OHT. Results. The induction of mN1(IC) by OHT resulted in reduction of prolifera tion (p < 0.01) and accumulation of cells in the G(1)/G(0) phase of the cel l cycle (p < 0.001) without substantially affecting apoptosis of 32D cells, These effects were observed under culture conditions that allow differenti ation 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 proliferatio n of myeloid progenitor cells by altering cell-cycle kinetics. (C) 2000 Int ernational Society far Experimental Hematology. Published by Elsevier Scien ce Inc.