1. ¹Centre Oncologia Molecular, IDIBELL-Institut de Recerca Oncològica, Hospitalet, Barcelona, Spain
2. ²Centro Andaluz Biología Desarrollo, CSIC, Universidad Pablo Olavide, Sevilla, Spain
3. ³Department Immunology and Oncology, Centro Nacional de Biotecnología, CSIC, Campus de Cantoblanco, Madrid, Spain

Correspondence: Dr A Bigas, Oncologia Molecular, IDIBELL-Institut de Recerca Oncològica, Gran Via Km 2.7, Hospitalet, Barcelona 08907 Spain. E-mail: abigas@iro.es

Received 29 January 2007; Revised 2 March 2007; Accepted 14 March 2007; Published online 3 May 2007.

Abstract

Programmed cell death plays an important role in erythropoiesis under physiological and pathological conditions. In this study, we show that the Notch/RBPj signaling pathway induces erythroid apoptosis in different hematopoietic tissues, including yolk sac and bone marrow as well as in murine erythroleukemia cells. In RBPj^-/- yolk sacs, erythroid cells have a decreased rate of cell death that results in increased number of Ter119+ cells. A similar effect is observed when Notch activity is abrogated by incubation with the -secretase inhibitors, DAPT or L685,458. We demonstrate that incubation with Jagged1-expressing cells has a proapoptotic effect in erythroid cells from adult bone marrow that is prevented by blocking Notch activity. Finally, we show that the sole expression of the activated Notch1 protein is sufficient to induce apoptosis in hexametilene-bisacetamide-differentiating murine erythroleukemia cells. Together these results demonstrate that Notch regulates erythroid homeostasis by inducing apoptosis.