Project description:The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in significant changes in gene expression. In contrast, deletion of either Gsk-3a or Gsk-3b individually had little effect on gene expression. These data support the notion that Gsk-3 isoforms are functionally redundant in embryonic stem cells. In addition, we did not find the expected upregulation of known Wnt target genes. Our data suggests that Gsk-3-meidated regulation of gene expression in embryonic stem cells is complex, and likely involves affects on numerous signaling pathways. The study was designed to examine the changes in gene expression between wild-type, Gsk-3a-/-, Gsk-3b-/-, and Gsk-3a-/-;Gsk-3b-/- mouse embryonic stem cells.
Project description:Decitabine (DEC) has a known DNA demethylating activity but also cause cytotoxicity through DNA damage. The two differing mechanisms of action confound studies investigating the effect of DNA demethylation in cancer treatment. The novel DNA methyltransferase 1 specific inhibitor GSK-3685032 causes loss of DNA methylation without DNA damage and offers the possibility to examine the molecular consequences of global loss of DNA methylation. EM-seq was used to evaluate the DNA demethylating effects of DEC and GSK-3685032 in LOUCY and SUP-T1 cells treated with 10 nM Decitabine for 3 days or 300 nM of GSK-3685032 for 3 and 7 days.
Project description:The goal of this study was to understand the transcriptional differences between UTX/JMJD3 DKO NKT precursors (P1) and WT litter mater controls. Two female and one male sample for each is included. 6 samples, 3 WT(2F, 1M), 3 DKO (2F, 1M)
