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

Brittany Nicole Weber, Anthony Wei-Shine Chi, Alejandro Chavez, Yumi Yashiro-Ohtani, Qi Yang, Olga Shestova and Avinash Bhandoola ()
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Brittany Nicole Weber: University of Pennsylvania School of Medicine
Anthony Wei-Shine Chi: University of Pennsylvania School of Medicine
Alejandro Chavez: University of Pennsylvania School of Medicine
Yumi Yashiro-Ohtani: University of Pennsylvania School of Medicine
Qi Yang: University of Pennsylvania School of Medicine
Olga Shestova: University of Pennsylvania School of Medicine
Avinash Bhandoola: University of Pennsylvania School of Medicine

Nature, 2011, vol. 476, issue 7358, 63-68

Abstract: 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.

Date: 2011
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DOI: 10.1038/nature10279

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