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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2879-2881. Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-05-1815.
Submitted May 4, 2005
Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, Ghent University Hospital, Ghent, Belgium * Corresponding author; email: georges.leclercq{at}ugent.be.
By retroviral overexpression of the Notch-1 intracellular domain (ICN) in human CD34+ HSCs, we have shown previously that Notch-1 signalling promotes the T-cell fate and inhibits the monocyte and B-cell fate in several in vitro and in vivo differentiation assays. Here, we investigated whether the effects of constitutively active Notch-1 can be mimicked by overexpression of its downstream target gene HES-1. Upon HES-1 retroviral transduction, human CD34+ stem cells had a different outcome in the differentiation assays as compared to ICN-transduced cells. Although HES-1 induced a partial block in B-cell development, it did not inhibit monocyte development and did not promote T/NK-cell lineage differentiation. On the contrary, a higher percentage of HES-1-transduced stem cells remained CD34+. These experiments indicate that HES-1 alone is not able to substitute for Notch-1 signalling to induce T-cell differentiation of human CD34+ hematopoietic stem cells.
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