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  • Original Paper
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Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations

Oncogene volume 21, pages 3855–3863 (2002)Cite this article

Abstract

To examine the effects of Notch signaling on hematopoiesis, we transplanted mice with progenitors transduced with a constitutively active form of Notch1 (Notch1IC) or the Notch1 target genes Hes. Notch1IC-transduced cells induce T cell tumors and cannot generate B lymphocytes in vivo. Hes-transplanted mice remained healthy but cells transduced with Hes1 or Hes5 were partially impaired in their ability to differentiate into B cells. Both Hes1 and Hes5 were upregulated in the BM of Notch1IC mice and their ability to interfere with the transcriptional activity of E2A in a reporter assay was comparable to that of Notch1IC. This suggests that the inhibition of B cell development in the Notch1IC-transduced cells could be mediated by the interference of HES1/HES5 proteins with E2A. Hes1-, Hes5- and Notch1IC-transduced bone marrow cells cultured ex vivo in a colony forming assay in the presence of cytokines that promote myeloid differentiation remained very immature, indicating that the myeloid potential of these bone marrow cells was altered. Thymocytes overexpressing Hes1, Hes5 or Notch1IC matured normally into CD4 and CD8 single positive cells in vivo. Altogether our data suggest that Notch1IC induces T cell tumors independently of Hes genes but that its interference with lymphoid B and myeloid maturation is partly mediated by Hes1 and Hes5.

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Acknowledgements

We thank Dr R Kageyama of Institute for Virus Research, Kyoto University for reagents and discussion, Drs AM O'Farrell, L Murray, D Chen, M Kondo and D Scherer for critical reading of the manuscript and input, Dr M Cleary of Stanford University School of Medicine for the Notch1IC cDNA, Drs IL Weissman of Stanford University School of Medicine and J Spangrude of Utah University School of Medicine for helpful suggestions.

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Author notes

  1. Shin Kawamata

    Present address: Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, 606-8507, Kyoto, Japan

  2. Catherine Lavau

    Present address: CNRS UPR 9051, Hôpital Saint-Louis 1, Ave. Claude Vellefaux, Paris, Cedex 10, 75475, France

Authors and Affiliations

  1. SyStemix Inc. 3155 Porter Dr. Palo Alto, 94304, California, CA, USA

    Shin Kawamata, Changchun Du & Catherine Lavau

  2. Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, 94305, California, CA, USA

    Kaijun Li

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  1. Shin Kawamata
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Correspondence to Catherine Lavau.

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Kawamata, S., Du, C., Li, K. et al. Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations. Oncogene 21, 3855–3863 (2002). https://doi.org/10.1038/sj.onc.1205487

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