Overexpression of HES-1 is not sufficient to impose T-cell differentiation on human hematopoietic stem cells
Copyright policy )Overexpression of HES-1 is not sufficient to impose T-cell differentiation on human hematopoietic stem cells
Abstract 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.
- Université Libre de Bruxelles Belgium
- Ghent University Hospital Belgium
- Ghent University Belgium
T-Lymphocytes -- cytology -- immunology, Retroviridae -- genetics, T-Lymphocytes, Antigens, CD34, Notch1 -- immunology, Monocytes, Transduction, Monocytes -- immunology, Genetic, Antigens, CD, Transduction, Genetic, Hematopoietic Stem Cells -- drug effects -- immunology, Cell Differentiation -- immunology, Basic Helix-Loop-Helix Transcription Factors, Humans, Gene Expression Regulation -- immunology, Antigens, Receptor, Notch1, Homeodomain Proteins, B-Lymphocytes, Homeodomain Proteins -- genetics -- immunology, Basic Helix-Loop-Helix Transcription Factors -- genetics -- immunology, Cell Differentiation, Hematopoietic Stem Cells, Cancérologie, CD -- immunology, Retroviridae, Gene Expression Regulation, CD34 -- immunology, Transcription Factor HES-1, B-Lymphocytes -- immunology, Receptor
T-Lymphocytes -- cytology -- immunology, Retroviridae -- genetics, T-Lymphocytes, Antigens, CD34, Notch1 -- immunology, Monocytes, Transduction, Monocytes -- immunology, Genetic, Antigens, CD, Transduction, Genetic, Hematopoietic Stem Cells -- drug effects -- immunology, Cell Differentiation -- immunology, Basic Helix-Loop-Helix Transcription Factors, Humans, Gene Expression Regulation -- immunology, Antigens, Receptor, Notch1, Homeodomain Proteins, B-Lymphocytes, Homeodomain Proteins -- genetics -- immunology, Basic Helix-Loop-Helix Transcription Factors -- genetics -- immunology, Cell Differentiation, Hematopoietic Stem Cells, Cancérologie, CD -- immunology, Retroviridae, Gene Expression Regulation, CD34 -- immunology, Transcription Factor HES-1, B-Lymphocytes -- immunology, Receptor
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