Project description:Rpl22l1 is a highly conserved ribosomal protein paralog that plays a regulatory role in certain hematopoietic cell lineages. Rpl22l1-deficiency arrests the development of T cells at the DN3 stage. RNA-seq analysis was performed to identify the molecular basis for the arrest
Project description:Lineage negative, CD44 negative, CD25 positive thymocytes were isolated from wt mice or Miz1 POZ-domain knockout mice to analyze the effect of loss of Miz1 in the DN3 population of T-cells We used the mouse Affymetrix MOE430-2 microarray to characterize global gene expression changes of DN3 thymocytes from Miz1 knockout mice.
Project description:Lineage negative, CD44 negative, CD25 positive thymocytes were isolated from wt mice or Miz1 POZ-domain knockout mice to analyze the effect of loss of Miz1 in the DN3 population of T-cells We used the mouse Affymetrix MOE430-2 microarray to characterize global gene expression changes of DN3 thymocytes from Miz1 knockout mice. We performed microarray based gene expression profiling to determine the effect of loss of Miz1 activity on the gene expression pattern of mouse DN3 thymocytes from wt and Miz1-delta-POZ mice.
Project description:T cell-specific overexpression of miR-185 caused a developmental block at DN3 stage of thymopoiesis. DN3 stage thymocytes were sorted from the wild type (C57BL/6) and miR-185 Tg mice, followed by total RNA isolation.
Project description:Mitochondria and endoplasmic reticulum contacts (MERCs) regulate multiple cellular processes including cell survival and differentiation. Based on the observations that MERCs were specifically enriched in the CD4-CD8- double negative (DN) stage, we studied their role in early thymocyte development. We found that T-cell-specific knockout of Hspa9, which encodes GRP75, a chaperone mediates MERC formation by assembling the IP3R-GRP75-VDAC complex, impaired DN3 thymocyte viability and resulted in thymocyte developmental arrest at the DN3-DN4 transition. Mechanistically, GRP75 deficiency induced mitochondrial stress, releasing mitochondrial DNA (mtDNA) into the cytosol and triggering the type I interferon (IFN-I) response. IFN-I pathway contributed to both the impairment of cell survival and DN3-DN4 transition blockage, while increased lipid peroxidation (LPO) played a major role downstream of IFN-I. Thus, our study reveals the essential role of GRP75-dependent MERCs in early thymocyte development and uncovers the governing facts of cellular survival and differentiation in the DN stage.
Project description:In this study we want to compare the gene expression profile of CD44+CXCR6+ CD8+ T cells from the liver of ND and CD-HFD mice with hepatic CD44+CXCR6neg and splenic CD44+ CX3CR1neg CD8 T cells of ND and CD-HFD mice. This comparison will reveal transcriptional signatures of hepatic CD44+CXCR6+ CD8+ T cells in CD-HFD responsible for causing liver pathology in NASH.