Abstract
Mice mutant for the bHLH gene Hes1, which is known to keep cells in a proliferative state, mostly lack thymus. Transfer of Hes1-null fetal liver cells into RAG2-null host mice normally reconstitutes B cells but fails to generate mature T cells in the thymus. In the reconstituted thymus, T cell differentiation is arrested at the CD4(-)CD8(-) double negative (DN) stage. Both the initial T cell receptor (TCR)-independent and the subsequent TCR-dependent selective expansion during the DN stage are severely affected. Thus, Hes1 is essential for the earliest thymocyte expansion in a cell-autonomous manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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CD4 Antigens / metabolism
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CD8 Antigens / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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DNA-Binding Proteins / genetics
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Gene Rearrangement, T-Lymphocyte
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Helix-Loop-Helix Motifs / genetics*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / immunology
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Homeodomain Proteins / genetics*
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Mice
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Mice, Knockout
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Mutation
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology
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Transcription Factor HES-1
Substances
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Basic Helix-Loop-Helix Transcription Factors
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CD4 Antigens
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CD8 Antigens
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DNA-Binding Proteins
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Hes1 protein, mouse
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Homeodomain Proteins
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Rag2 protein, mouse
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Transcription Factor HES-1
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V(D)J recombination activating protein 2