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

• DOI: 10.1073/pnas.0601188103
• Publication Date: 2006-08-02T07:50:15Z
• Authors: Christopher B. Fr...; Deirdre D. Script...; Irina Proekt; Tom Taghon; Angela H. Weiss; Mary A. Yui; Stephanie L. Adams; Rochelle A. Diamond; Ellen V. Rothenberg
• Keywords: 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

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.