Project description:The NOTCH1 signaling pathway is a critical determinant of cell fate decisions and drives oncogenesis through mechanisms that are incompletely understood. To elucidate tumorigenic pathways that cooperate with activated Notch1 in leukemogenesis,we performed miRNA expression profiling of normal CD4+CD8+ thymocytes, non-malignant ICN1 over-expressing CD4+CD8+ cells and ICN1-induced tumor CD4+CD8+ cells. Three groups of the murine T cells: Control CD4+CD8+ normal thymocytes vs.non-malignant ICN1-expressing CD4+CD8+ cells vs. ICN1-tumor CD4+CD8+ cells .
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
