How transcription factors drive choice of the T cell fate

Nat Rev Immunol. 2021 Mar;21(3):162-176. doi: 10.1038/s41577-020-00426-6. Epub 2020 Sep 11.

Abstract

Recent evidence has elucidated how multipotent blood progenitors transform their identities in the thymus and undergo commitment to become T cells. Together with environmental signals, a core group of transcription factors have essential roles in this process by directly activating and repressing specific genes. Many of these transcription factors also function in later T cell development, but control different genes. Here, we review how these transcription factors work to change the activities of specific genomic loci during early intrathymic development to establish T cell lineage identity. We introduce the key regulators and highlight newly emergent insights into the rules that govern their actions. Whole-genome deep sequencing-based analysis has revealed unexpectedly rich relationships between inherited epigenetic states, transcription factor-DNA binding affinity thresholds and influences of given transcription factors on the activities of other factors in the same cells. Together, these mechanisms determine T cell identity and make the lineage choice irreversible.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Lineage / genetics
  • Cell Lineage / immunology*
  • Epigenesis, Genetic / genetics
  • Genome / genetics
  • Humans
  • Mice
  • Receptors, Notch / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transcription Factors / metabolism*
  • Whole Genome Sequencing

Substances

  • Receptors, Notch
  • Transcription Factors