An essential developmental checkpoint for production of the T cell lineage

Science. 2010 Jul 2;329(5987):93-6. doi: 10.1126/science.1188995.

Abstract

In early T cell development, progenitors retaining the potential to generate myeloid and natural killer lineages are eventually determined to a specific T cell lineage. The molecular mechanisms that drive this determination step remain unclarified. We show that, when murine hematopoietic progenitors were cultured on immobilized Notch ligand DLL4 protein in the presence of a cocktail of cytokines including interleukin-7, progenitors developing toward T cells were arrested and the arrested cells entered a self-renewal cycle, maintaining non-T lineage potentials. Reduced concentrations of interleukin-7 promoted T cell lineage determination. A similar arrest and self-renewal of progenitors were observed in thymocytes of mice deficient in the transcription factor Bcl11b. Our study thus identifies the earliest checkpoint during T cell development and shows that it is Bcl11b-dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage*
  • Cells, Cultured
  • Coculture Techniques
  • Gene Expression Regulation, Developmental
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Interleukin-7 / metabolism
  • Liver / embryology
  • Lymphopoiesis* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Precursor Cells, T-Lymphoid / cytology
  • Precursor Cells, T-Lymphoid / physiology*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / physiology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation

Substances

  • Bcl11b protein, mouse
  • Interleukin-7
  • Repressor Proteins
  • Tumor Suppressor Proteins