Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBP alpha and PU.1 transcription factors

Immunity. 2006 Nov;25(5):731-44. doi: 10.1016/j.immuni.2006.09.011.


The differentiation potential of T lineage cells becomes restricted soon after entry of multipotent precursors into the thymus and is accompanied by a downregulation of the transcription factors C/EBP alpha and PU.1. To investigate this restriction point, we have expressed C/EBP alpha and PU.1 in fully committed pre-T cells and found that C/EBP alpha (and C/EBP beta) induced the formation of functional macrophages. In contrast, PU.1 converted them into myeloid dendritic cells under identical culture conditions. C/EBP alpha-induced reprogramming is complex because upregulation of some but not all myelomonocytic markers required endogenous PU.1. Notch signaling partially inhibited C/EBP alpha-induced macrophage formation and completely blocked PU.1-induced dendritic cell formation. Likewise, expression of intracellular Notch or the transcription factor GATA-3 inhibited C/EBP alpha-induced lineage conversion. Our data show that committed T cell progenitors remain susceptible to the lineage instructive effects of myeloid transcription factors and suggest that Notch signaling induces T lineage restriction by downregulating C/EBP alpha and PU.1 in multilineage precursors.

Publication types

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

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / immunology*
  • Cell Differentiation / immunology
  • Cell Lineage / immunology
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Gene Expression / immunology
  • Gene Expression Regulation / immunology
  • Macrophages / cytology*
  • Macrophages / immunology
  • Mice
  • Proto-Oncogene Proteins / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology*
  • Stem Cells / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Trans-Activators / immunology*


  • CCAAT-Enhancer-Binding Protein-alpha
  • Proto-Oncogene Proteins
  • Trans-Activators
  • proto-oncogene protein Spi-1