The amino acid homocysteine increases in the serum when there is insufficient folic acid or vitamin B12, or with certain mutations in enzymes important in methionine metabolism. Elevated homocysteine is related to increased risk for cardiovascular and other diseases in adults and elevated maternal homocysteine increases the risk for certain congenital defects, especially those that result from abnormal development of the neural crest and neural tube. Experiments with the avian embryo model have shown that elevated homocysteine perturbs neural crest / neural tube migration in vitro and in vivo. While there have been numerous studies of homocysteine-induced changes in gene expression in adult cells, there is no previous report of a homocysteine-responsive transcriptome in the embryonic neural crest. We treated neural crest cells in vitro with exogenous homocysteine in a protocol that induces significant changes in neural crest cell migration. We used microarray analysis and expression profiling to identify 65 transcripts of genes of known function that were altered by homocysteine. The largest set of effected genes (19) included those with a role in cell migration and adhesion. Other major groups were genes involved in metabolism (13); DNA / RNA interaction (11); cell proliferation / apoptosis (10); and transporter / receptor (6). Although the genes identified in this experiment were consistent with prior observations of the effect of homocysteine upon neural crest cell function, none had been identified previously as response to homocysteine in adult cells.
Microarray analysis of homocysteine-responsive genes in cardiac neural crest cells in vitro.
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View SamplesPurpose:To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Methods: We employed piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL. Overall design: To address if the fludarabine-resistant HG3 cells were transcriptionally different at a global level compared to their parental cells, we performed RNA-sequencing of three pairs of HG3 pools
Transposon Mutagenesis Reveals Fludarabine Resistance Mechanisms in Chronic Lymphocytic Leukemia.
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View SamplesWe identified differential gene expression after treatment with BRD4-PROTAC ARV771 in two ABC-like diffuse large B-cella lymphoma cell lines. We have identified cluster of gene expression regulated after BRD4 inhibition which are criticaly important for DLBCL malignancy. Overall design: Two ABC-DLBCL cell lines were used to identify the changes in gene expression profile after BRD4-PROTAC (ARV771) treatment.
Targetable genetic alterations of <i>TCF4</i> (<i>E2-2</i>) drive immunoglobulin expression in diffuse large B cell lymphoma.
Specimen part, Cell line, Treatment, Subject
View SamplesAlthough liganded nuclear receptors have been established to regulate RNA polymerase II (Pol II)-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here we report that ~2-3% of the ~100,000-200,000 total human DR2 Alu repeats located in proximity to activated Pol II transcription units are activated by the retinoic acid receptor (RAR) in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in a DICER-dependent fashion, into small RNAs (~28-65 nt) referred to as repeat-induced RNAs that cause the degradation of a subset of crucial stem-cell mRNAs, including Nanog mRNA, which modulate exit from the proliferative stem-cell state. This regulation requires AGO3-dependent accumulation of processed DR2 Alu transcripts and the subsequent recruitment of AGO3-associated decapping complexes to the target mRNA. In this way, the RAR-dependent and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program. Overall design: RNA-sequencing of polyA selected RNA molecules in NTera2/D1 cells and Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq).
DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation.
Specimen part, Treatment, Subject
View SamplesThe experiment aims to identify transcriptional effects of Infliximab (an anti-TNF antibody) and CDP870 on human cell lines
mTNF reverse signalling induced by TNFα antagonists involves a GDF-1 dependent pathway: implications for Crohn's disease.
Cell line, Treatment, Time
View SamplesAdult zebrafish are capable of regenerating cardiac tissue following ventricular resection within 30 days. We profiled both small RNA and mRNA expression in uninjured (0dpa), 1, 3, 7, 14, 21 and 30 days post amputation to study biological processes orchestrate each stage of regeneration. Overall design: Small and mRNA gene expression profiling during 0, 1, 3, 7, 14, 21 and 30 days post ventricular resection.
RegenDbase: a comparative database of noncoding RNA regulation of tissue regeneration circuits across multiple taxa.
Specimen part, Cell line, Subject
View SamplesAdam17, a shedding protease, is strongly upregtulated during inflammation and cancer. Here we investigate the genome wide effects of Adam17 knock out on the transcriptome.
Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice.
Specimen part
View SamplesTo identify genes that are regulated from the lncRNA ANRIL (EXON 13), we designed inducible short hairpin RNA constructs and stable integrated them into HEK cells
The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10.
Disease
View SamplesTo identify genes that are regulated from the lncRNA ANRIL (EXON19), we designed inducible short hairpin RNA constructs and stable integrated them into HEK cells
Linear isoforms of the long noncoding RNA CDKN2B-AS1 regulate the c-myc-enhancer binding factor RBMS1.
Disease
View SamplesThyroid hormone receptors (TRs) are hormone-regulated transcription factors that regulate a diverse array of biological activities, including metabolism, homeostasis, and development. TRs also serve as tumor suppressors, and aberrant TR function (via mutation, deletion, or altered expression) is associated with a spectrum of both neoplastic and endocrine diseases. A particularly high frequency of TR mutations has been reported in renal clear cell carcinoma (RCCC) and in hepatocellular carcinoma (HCC). We have shown that HCC-TR mutants regulate only a fraction of the genes targeted by wild-type TRs, but have gained the ability to regulate other, unique, targets. We have suggested that this altered gene recognition may contribute to the neoplastic phenotype. Here, to determine the generality of this phenomenon, we examined a distinct set of TR mutants associated with RCCCs. We report that two different TR mutants, isolated from independent RCCC tumors, possess greatly expanded target gene specificities that extensively overlap one another, but only minimally overlap that of the WT-TRs, or those of two HCC-TR mutants. Many of the genes targeted by either or both RCCC-TR mutants have been previously implicated in RCCC, and include a series of metallothioneins, solute carriers, and genes involved in glycolysis and energy metabolism. We propose that TR mutations from RCCC and HCC are likely to play tissue-specific roles in carcinogenesis, and that the divergent target gene recognition patterns of TR mutants isolated from the two different types of tumors arises from different selective pressures during development of RCCC versus HCC.
Mutant thyroid hormone receptors (TRs) isolated from distinct cancer types display distinct target gene specificities: a unique regulatory repertoire associated with two renal clear cell carcinomas.
Disease, Cell line, Treatment
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