Overexpression of HES-1 is not sufficient to impose T-cell differentiation on human hematopoietic stem cells.
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.
Hoebeke
Inge
I
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, 4 Blok A, De Pintelaan 185, B-9000 Ghent, Belgium.
De Smedt
Magda
M
Van de Walle
Inge
I
Reynvoet
Katia
K
De Smet
Greet
G
Plum
Jean
J
Leclercq
Georges
G
D015703:Antigens, CD / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology; D051881:Receptor, Notch1 / Q000276:immunology*; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D000072056:Transcription Factor HES-1; D014161:Transduction, Genetic
D015703:Antigens, CD; D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C497761:NOTCH1 protein, human; C078493:HES1 protein, human