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A critical role for TCF-1 in T-lineage specification and differentiation.
- Source :
-
Nature [Nature] 2011 Aug 03; Vol. 476 (7358), pp. 63-8. Date of Electronic Publication: 2011 Aug 03. - Publication Year :
- 2011
-
Abstract
- The vertebrate thymus provides an inductive environment for T-cell development. Within the mouse thymus, Notch signals are indispensable for imposing the T-cell fate on multipotential haematopoietic progenitors, but the downstream effectors that impart T-lineage specification and commitment are not well understood. Here we show that a transcription factor, T-cell factor 1 (TCF-1; also known as transcription factor 7, T-cell specific, TCF7), is a critical regulator in T-cell specification. TCF-1 is highly expressed in the earliest thymic progenitors, and its expression is upregulated by Notch signals. Most importantly, when TCF-1 is forcibly expressed in bone marrow (BM) progenitors, it drives the development of T-lineage cells in the absence of T-inductive Notch1 signals. Further characterization of these TCF-1-induced cells revealed expression of many T-lineage genes, including T-cell-specific transcription factors Gata3 and Bcl11b, and components of the T-cell receptor. Our data suggest a model where Notch signals induce TCF-1, and TCF-1 in turn imprints the T-cell fate by upregulating expression of T-cell essential genes.
- Subjects :
- Animals
Female
Genes, Essential
HEK293 Cells
Hepatocyte Nuclear Factor 1-alpha
Humans
Lymphoid Enhancer-Binding Factor 1 metabolism
Male
Mice
Mice, Inbred C57BL
Receptor, Notch1 metabolism
Signal Transduction
T Cell Transcription Factor 1 deficiency
T Cell Transcription Factor 1 genetics
Up-Regulation
Cell Differentiation
Cell Lineage
T Cell Transcription Factor 1 metabolism
T-Lymphocytes cytology
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 476
- Issue :
- 7358
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 21814277
- Full Text :
- https://doi.org/10.1038/nature10279