title: Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBP alpha and PU.1 transcription factors.
abstract: 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.
authors.affiliation: Department of Developmental and Molecular Biology and the Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Catherine V
authors.initials: CV
authors.lastname: Laiosa
authors.forename: Matthias
authors.initials: M
authors.lastname: Stadtfeld
authors.forename: Huafeng
authors.initials: H
authors.lastname: Xie
authors.forename: Luisa
authors.initials: L
authors.lastname: de Andres-Aguayo
authors.forename: Thomas
authors.initials: T
authors.lastname: Graf
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015534:Trans-Activators / Q000276:immunology*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1