Project description:Despite the function of Myc oncogene has been extensively studied, little is known concerning its role in Natural killer (NK) cells. By performing RNA-sequencing analyses comparing Myc-deficient to Myc-sufficient NK cells, we aim at determining the biological function of Myc in these innate lymphocytes.
Project description:To understand the mechanism of the defective NK cell functions with MYC deficiency, we isolated splenic NK cells (CD3-NK1.1+CD49b+) from Mycf/f and MycΔ/Δ/Ncr1Cre mice and performed RNA-seq analysis. It revealed that ribosome and natural killer cell-mediated cytotoxicity were the two most enriched pathways in the differentially down-regulated genes. Functional studies showed reduced synthesis of NK cell effector molecules in the NK Cells with MYC deficiency. Collectively, these data suggest impaired ribosomal biogenesis and reduced synthesis of cytotoxic molecule in the NK cells with MYC deficiency.
Project description:Impact of CDK4-deficiency on EM-BM-5-myc driven B-lymphoma By crossing mating CDK4 Knockout mice with EM-BM-5-myc mice,We found CDK4-deficiency enhances the EM-BM-5-myc induced B-lymphoma.We further to discover the molecular mechanism B-lymphoma cells form the cdk4+/+ EM-BM-5-myc and cdk4-/-EM-BM-5-myc mice and then culturing for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Impact of CDK4-deficiency on Eµ-myc driven B-lymphoma By crossing mating CDK4 Knockout mice with Eµ-myc mice,We found CDK4-deficiency enhances the Eµ-myc induced B-lymphoma.We further to discover the molecular mechanism
Project description:Classical NK cells are the prototypical type 1 innate lymphocytes mounting cytolytic and IFNg responses to intracellular pathogens and tumors. A similar but distinct population termed ILC1 was recently described, differing from NK cells in multiple though relatively subtle ways, including tissue residency vs recirculation, and levels of NK receptors. Whether the differences reflect distinct lineages or mere variations in program expression is not fully understood. Here, using transcription factor reporter mice and cell transfers of bone marrow precursors, we found that, upon transfer in vivo, Eomes-expressing, lineage-negative, NK receptor-negative cells acquired properties typically associated with classical NK cells including the capacity to prevent metatstatic disease. In contrast, as previously reported, PLZFhigh cells mostly generated ILC1, ILC2, or ILC3. These findings identify the Eomes-expressing NK precursor as the long-elusive bone marrow precursor to classical NK cells, and demonstrate that the NK and ILC1 lineages diverge early during development.
Project description:Natural killer (NK) cells are critical mediators of host immunity against infectious disease and cancer. The intrinsic regulators of NK cells are not fully understood. Here, we demonstrate that the ER stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) critically drive NK cell-mediated responses against viral infection and tumors. IRE1α and XBP1 were essential for the robust expansion of activated mouse and human NK cells. Transcriptome analysis revealed the transcription factor c-Myc as a novel and direct target of XBP1 for downstream regulation of NK cell proliferation. Genetic ablation or pharmaceutical blockade of IRE1α downregulated c-Myc, whereas overexpression of XBP1 resulted in c-Myc hyperactivation. NK cells lacking c-Myc demonstrated a functional deficit comparable to IRE1α or XBP1 deficiency. Overall, our study identifies a novel IRE1-XBP1-cMyc axis in NK cell immunity, providing new insight into the host immune response against infection and cancer.