This SuperSeries is composed of the SubSeries listed below.
Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma.
Specimen part
View SamplesGlobal gene expression in TET2 mutant and Wild type patients. We performed an integrated analysis of global DNA methylation and gene expression data to investigate the effects of DNA hypermethylation on gene expression.
Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Loss of PRDM11 promotes MYC-driven lymphomagenesis.
Specimen part, Cell line
View SamplesThe PR-domain family (PRDMs) encodes transcriptional regulators, several of which are deregulated in cancer. We found that loss of Prdm11 accelerates MYC-driven lymphomagenesis in the E-Myc mouse model.
Loss of PRDM11 promotes MYC-driven lymphomagenesis.
Specimen part
View SamplesThe PR-domain family e(PRDMs) encodes transcriptional regulators, several of which are deregulated in cancer. We found that loss of Prdm11 accelerates MYC-driven lymphomagenesis in the Eµ-Myc mouse model. Moreover, we show that patients with PRDM11-deficient diffuse large B cell lymphomas (DLBCLs) have poorer overall survival and belong to the non-Germinal Center B cell (GCB)-like subtype. Mechanistically, genome-wide mapping of PRDM11 binding sites coupled with transcriptome sequencing in human DLBCL cells evidenced that PRDM11 associates with transcriptional start sites of target genes and regulates important oncogenes such as FOS and JUN. Hence, we characterize PRDM11 as a novel tumor suppressor controlling the expression of key oncogenes and add new mechanistic insight into B-cell lymphomagenesis. Overall design: RNA-seq performed after knockdown of Prdm11
Loss of PRDM11 promotes MYC-driven lymphomagenesis.
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View SamplesBivalent histone domains have been proposed to contribute to pluripotency in embryonic stem cells, suggesting an epigenetic mechanism may regulate stem cell behavior in general. Here we compare histone modifications in two other stem cells derived from the blastocyst. We show that extraembryonic stem cells have little repressive lysine 27 trimethylation and few bivalent domains. Thus, bivalent domains are not a common mechanism for maintaining the undifferentiated state in blastocyst-derived stem cells and alternative mechanisms must mediate transcriptional repression in extraembryonic cells. We show that lysine 9 trimethylation, but not DNA methylation, is likely to fulfill this role. Intriguingly, although we do detect bivalent domains in pluripotent cells in the early mouse embryo, the epigenetic status of extraembryonic cells does not entirely reflect their in vitro stem cell counterparts. Therefore, differences in epigenetic regulation between lineage progenitors in vivo and in vitro may arise during selection for self-renewal in vitro.
Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo.
Cell line
View SamplesWhile the reprogramming factors OCT4, SOX2, KLF4, and MYC (OSKM) can reactivate the pluripotency network in terminally differentiated cells, they also regulate expression of non-pluripotency genes in other contexts, such as the mouse primitive endoderm. The primitive endoderm is an extraembryonic lineage established alongside the pluripotent epiblast in the blastocyst, and is the progenitor pool for extraembryonic endoderm stem (XEN) cells. Several studies have shown that endodermal genes are upregulated in fibroblasts undergoing reprogramming, although whether endodermal genes promote or inhibit acquisition of pluripotency is unclear. We show that, in fibroblasts undergoing conventional reprogramming, OSKM-induced expression of endodermal genes leads to formation of induced XEN (iXEN) cells, which possess key properties of blastocyst-derived XEN cells, including morphology, transcription profile, self-renewal, and multipotency. Our data show that iXEN cells arise in parallel to iPS cells, indicating that OSKM are sufficient to drive cells to two distinct fates during reprogramming. Overall design: Sequence-based mRNA transcriptional profiling of three different cell lines (MEF, XEN, iXEN) with multiple biological replicates, under two different growth medium conditions (ESC medium, XEN medium) for XEN and iXEN cells.
OSKM Induce Extraembryonic Endoderm Stem Cells in Parallel to Induced Pluripotent Stem Cells.
Specimen part, Treatment, Subject
View SamplesStearoyl-CoA desaturase (SCD) is the rate-limiting enzyme catalyzing the conversion of saturated fatty acids palmitate and stearate to monounsaturated fatty acids palmitoleate and oleate. During adipocyte differentiation, SCD expression increases concomitantly with several transcription factors and lipogenic genes.
Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes upregulates elongase 6 and downregulates genes affecting triacylglycerol synthesis.
Specimen part, Treatment
View SamplesSaturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA).
Individual saturated and monounsaturated fatty acids trigger distinct transcriptional networks in differentiated 3T3-L1 preadipocytes.
Specimen part
View SamplesES cell lines were established from mouse embryos, which were homozygous for the Trim33-flox allele and carried the UbcCreERT2 transgene. Cells were cultured without feeder cells in the presence of LIF and 2i. Embryoid bodies (EBs) were generated using the ATCC protocol on low attachment dishes under differentiating conditions. EBs were induced with Tamoxifen at day 4 and harvested at day 7. Overall design: Investigate differentially expressed genes in control and Trim33-deficient embryoid bodies derived from mouse embryonic stem cells
Trim33 is required for appropriate development of pre-cardiogenic mesoderm.
Specimen part, Cell line, Subject, Time
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