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

BN Weber, AWS Chi, A Chavez, Y Yashiro-Ohtani… - Nature, 2011 - nature.com
Nature, 2011nature.com
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 …
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.
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