Notch/Delta signaling constrains reengineering of pro-T cells by PU.1

0301 basic medicine 570 Cell Survival T-Lymphocytes 610 lineage commitment Mice, Transgenic Models, Biological Mice 03 medical and health sciences transcription factors Proto-Oncogene Proteins Animals Cell Lineage Receptor, Notch1 T cell development Receptors, Interleukin-2 hematopoiesis Mice, Inbred C57BL Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 Trans-Activators gene regulation Caltech Library Services Signal Transduction
DOI: 10.1073/pnas.0601188103 Publication Date: 2006-08-02T07:50:15Z
ABSTRACT
PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated expression inhibits pro-T survival, proliferation, passage through β-selection by blocking transcription factors, signaling molecules, Rag gene expression, which a rearranged antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells protected from this may even undergo β-selection, as shown transduction defined subsets fetal thymocytes with differentiation in OP9-DL1 OP9 control cultures. The outcome these depends on Notch/Delta signaling. can efficiently divert toward myeloid-like state multigene regulatory changes, vetoes Gene analysis distinguishes sets critical lineage genes different combinatorial responses to signals, suggesting particular importance inhibition E proteins, Myb, and/or Gfi1 (growth factor independence 1) Notch only protects against diversion that have undergone specification after Thy-1 CD25 up-regulation. results imply precursors, normally acts modulate channel transcriptional activities during the until commitment.
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