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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.

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IMMUNOBIOLOGY
Brief report

Overexpression of HES-1 is not sufficient to impose T-cell differentiation on human hematopoietic stem cells

Inge Hoebeke, Magda De Smedt, Inge Van de Walle, Katia Reynvoet, Greet De Smet, Jean Plum, and Georges Leclercq

From the Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, Ghent University Hospital, Belgium.

By retroviral overexpression of the Notch-1 intracellular domain (ICN) in human CD34+ hematopoietic stem cells (HSCs), we have shown previously that Notch-1 signaling 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 HES1. 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 signaling to induce T-cell differentiation of human CD34+ hematopoietic stem cells.


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