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

0301 basic medicine 570 Cell Survival T-Lymphocytes T cell development 610 lineage commitment Mice, Transgenic Receptors, Interleukin-2 Models, Biological hematopoiesis Mice, Inbred C57BL Mice 03 medical and health sciences Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 transcription factors Proto-Oncogene Proteins Trans-Activators Animals Cell Lineage Receptor, Notch1 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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (34)
CITATIONS (94)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....