The cellular origin of chronic lymphocytic leukemia (CLL) is debated. Transcriptome analysis of CLL and normal peripheral blood and splenic B cell subsets displayed highest similarity of CLL to mature CD5+ B cells. We identified a distinct CD5+CD27+ post-germinal center B cell subset, and revealed that immunoglobulin V gene mutated CLL are more similar to mutated CD5+ B cells, whereas unmutated CLL are more related to unmutated CD5+ B cells. Stereotyped immunoglobulin V gene rearrangements were significantly enriched among CD5+ B cells, providing further genetic evidence for a derivation of CLL from CD5+ B cells. Moreover, we identified deregulated expression patterns providing novel insights into the pathophysiology of CLL, including downregulation of EBF1 and KLF family members.
Cellular origin and pathophysiology of chronic lymphocytic leukemia.
Specimen part
View SamplesWe assessed genome-wide expression of available pretreatment specimens from CLL patients enrolled in REACH, a study of fludarabine and cyclophosphamide FC or R-FC (addition of rituximab to FC) in relapsed CLL, to understand the disease heterogeneity and explore genes that may be prognostic or predictive of benefit from R-FC treatment. REACH (NCT00090051) was registered at www.clinicaltrials.gov.
PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia.
Specimen part, Disease stage, Subject
View SamplesThe mRNA processing body is a cellular structure that regulates the stability of cytoplasmic mRNA. MARF1/LMKB is an RNA-binding protein that is associated with maintenance of mRNA homeostasis and genomic stability. To investigate the function of LMKB in a human B lymphocyte cell line, BJAB cells were treated with either control lentivirus or a lentivirus containing LMKB siRNA.
LMKB/MARF1 localizes to mRNA processing bodies, interacts with Ge-1, and regulates IFI44L gene expression.
Specimen part, Cell line
View SamplesExpression .CEL files from Affymetrix HG-U133A 2.0 arrays using DNA from 14 human cell lines derived from metastasized melanoma
Differences in global gene expression in melanoma cell lines with and without homozygous deletion of the CDKN2A locus genes.
Specimen part, Cell line
View SamplesProstate cancer is the most commonly diagnosed malignancy in the United States. While the majority of cases are cured with radiation or surgery, about 1/3 of patients will develop metastatic disease which there is no cure, and has a life expectancy of less than 5 years. Identification of antigens associated with this transition to metastatic disease is crucial for future therapies. One such antigen of interest is the SSX gene family, which are cancer/testis antigens that are associated with the epithelial to mesenchymal transition in other cancer types. Prior work has shown that, in prostate cancer, SSX expression was restricted to metastatic tissue and not primary tumor tissue which may indicate a role in disease progression. Some work has been done into the function of the SSX family, which revealed transcriptional regulator activity. But neither the targets of this activity or the function of SSX are known. Through a transcriptomics approach, we are seeking a better understanding of the different genes and pathways SSX regulates in the context of prostate cancer, and to determine if these pathways may contribute to disease progression.
SSX2 regulates focal adhesion but does not drive the epithelial to mesenchymal transition in prostate cancer.
Cell line
View SamplesPrimary human hepatocytes (PHH) are a main instrument in drug metabolism research and in the prediction of drug-induced phase I/II enzyme induction in humans. The HepG2 liver-derived cell line is commonly used as a surrogate for human hepatocytes, but their use in ADME and toxicity studies can be limited because of lowered basal levels of metabolizing enzymes. Despite their widespread use, the transcriptome of HepG2 cells compared to PHH is not well characterized. In this study, microarray analysis was conducted to ascertain the differences and similarities in mRNA expression between HepG2 cells and human hepatocytes before and after exposure to a panel of fluoroquinolone compounds. Comparison of the nave HepG2 cell and PHH transcriptomes revealed a substantial number of basal gene expression differences. When HepG2 cells were dosed with a series of fluoroquinolones, trovafloxacin, which has been associated with human idiosyncratic hepatotoxicity, induced substantially more gene expression changes than the other quinolones, similar to previous observations with PHH. While TVX-treatment resulted in many gene expression differences between HepG2 cells and PHH, there were also a number of TVX-induced commonalities, including genes involved in RNA processing and mitochondrial function. Taken together, these results provide insight for interpretation of results from drug metabolism and toxicity studies conducted with HepG2 cells in lieu of PHH, and could provide further insight into the mechanistic evaluation of TVX-induced hepatotoxicity.
Trovafloxacin-induced gene expression changes in liver-derived in vitro systems: comparison of primary human hepatocytes to HepG2 cells.
Sex, Specimen part
View SamplesIn this study we have examined the effect of sub-cytotoxic exposure to aristolochic acids (1.65M) at 6h, 24h and 72h on the whole-genome expression profile in a rat proximal renal tubule cell line (NRK-52E).
Aristolochic acids - Induced transcriptomic responses in rat renal proximal tubule cells in vitro.
Cell line, Time
View SamplesViral infection can dramatically alter a cell''s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in production of viral gene transcripts -- viral transcripts compose less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, and this gene absence partially explains variation in viral transcriptional load. Despite variation in total viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells. Overall design: Dataset consists of a total of five single-cell datasets generated using the 10x Genomics Chromium Single Cell 3'' Solution platform. All samples were generated from a tissue culture infection model using A549 cells from ATCC and Influenza A/WSN/1933 virus. Uninfected control sample identically processed. Infected samples were generated from cells infected for 6, 8, and 10 hours with a single replicate at 8 hours.
Extreme heterogeneity of influenza virus infection in single cells.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Specimen part, Disease, Disease stage, Subject
View SamplesTo acquire a better understanding of the molecular pathogenesis of HS, we performed mRNA microarray studies to compare gene expression in lesional skin to healthy skin of HS patients.
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Subject
View Samples