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Apoptosis

The notch pathway positively regulates programmed cell death during erythroid differentiation

Leukemia volume 21, pages 1496–1503 (2007)Cite this article

Abstract

Programmed cell death plays an important role in erythropoiesis under physiological and pathological conditions. In this study, we show that the Notch/RBPjκ signaling pathway induces erythroid apoptosis in different hematopoietic tissues, including yolk sac and bone marrow as well as in murine erythroleukemia cells. In RBPjκ−/− 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 γ-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.

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Acknowledgements

We thank Liheng Li for Jagged1 plasmid, Raphael Kopan for N1ΔE plasmid and M Caudy for the hes1 plasmid. Thanks to I Fabregat and J Gil for extremely helpful suggestions and reagents. Many thanks to L Riera and J Inglés-Esteve for critical comments of the manuscript. We thank E Castaño from Serveis Cientifico-Tècnics, UB-Bellvitge, and J Petriz for flow cytometry technical support. LE is an investigator from the Carlos III program (ISCIII/02/3027). ARM is a recipient of a CIRIT predoctoral fellowship (2002-SI00791). This work was supported by the grants from Ministerio de Educación y Ciencia (SAF2004-03/98) and (SAF205-23978-E) and (SAF2003-07214).

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Authors and Affiliations

  1. Centre Oncologia Molecular, IDIBELL-Institut de Recerca Oncològica, Hospitalet, Barcelona, Spain

    À Robert-Moreno, L Espinosa & A Bigas

  2. Centro Andaluz Biología Desarrollo, CSIC, Universidad Pablo Olavide, Sevilla, Spain

    M J Sanchez

  3. Department Immunology and Oncology, Centro Nacional de Biotecnología, CSIC, Campus de Cantoblanco, Madrid, Spain

    J L de la Pompa

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Correspondence to A Bigas.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Robert-Moreno, À., Espinosa, L., Sanchez, M. et al. The notch pathway positively regulates programmed cell death during erythroid differentiation. Leukemia 21, 1496–1503 (2007). https://doi.org/10.1038/sj.leu.2404705

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