A critical role for TCF-1 in T-lineage specification and differentiation

Nature. 2011 Aug 3;476(7358):63-8. doi: 10.1038/nature10279.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Lineage*
  • 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
  • T Cell Transcription Factor 1 / metabolism*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism*
  • Up-Regulation


  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Notch1 protein, mouse
  • Receptor, Notch1
  • T Cell Transcription Factor 1

Associated data

  • GEO/GSE26559
  • GEO/GSE26560