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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Brittany Nicole Weber & Anthony Wei-Shine Chi & Alejandro Chavez & Yumi Yashiro-Ohtani & Qi Yang & Olga Shestova & Avinash Bhandoola, 2011. "A critical role for TCF-1 in T-lineage specification and differentiation," Nature, Nature, vol. 476(7358), pages 63-68, August.
    • Handle: RePEc:nat:nature:v:476:y:2011:i:7358:d:10.1038_nature10279
    DOI: 10.1038/nature10279
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    Cited by:

    1. Mei Wang & Chi Zhang, 2020. "Low LEF1 expression is a biomarker of early T-cell precursor, an aggressive subtype of T-cell lymphoblastic leukemia," PLOS ONE, Public Library of Science, vol. 15(5), pages 1-9, May.

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