Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus
| Autor: | Irwin D. Bernstein, Mari H. Dallas, Keizo Kato, Barbara Varnum-Finney |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Hematopoiesis and Stem Cells T-Lymphocytes Immunology HES5 Notch signaling pathway Cell Count Thymus Gland Biology Ligands Biochemistry Mice T-Lymphocyte Subsets Internal medicine Basic Helix-Loop-Helix Transcription Factors medicine Animals Humans RNA Messenger HES1 Progenitor cell B cell Regulation of gene expression B-Lymphocytes Receptors Notch Stem Cells Intracellular Signaling Peptides and Proteins Membrane Proteins Cell Biology Hematology T lymphocyte Cell biology Repressor Proteins Endocrinology medicine.anatomical_structure Gene Expression Regulation Stem cell |
| Zdroj: | Blood. 111:2615-2620 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2007-03-079855 |
| Popis: | Notch signaling establishes boundaries in the thymus by inducing T-cell commitment and inhibiting a B-cell choice. Here, we show a significant 1.6-fold increased generation of B-cell precursors in thymuses from mice deficient for Notch target Hes5 compared with wild-type littermates. We further show that culture of bone marrow–derived progenitors with increasing densities of purified immobilized Notch ligand (Delta1ext-IgG) induced increased expression of Notch targets Hes1 and Hes5, and that although Hes5-deficient progenitors responded appropriately to high densities of ligand, they misread intermediate and low densities. Together, our results suggest that to ensure an appropriate outcome in the thymus in response to a lower threshold of induced Notch signaling, induction of the additional target Hes5 is required. |
| Databáze: | OpenAIRE |
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