Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. We cultured cells in uniform conditions and profiled genome-wide copy numbers, mRNAs, proteins and protein turnover rates in each cell line. We discovered substantial heterogeneity between HeLa variants, especially between lines of the CCL2 and Kyoto varieties, and observed progressive divergence within a specific cell line over 50 successive passages. Genomic variability has a complex, nonlinear effect on transcriptome, proteome and protein turnover profiles, and proteotype patterns explain the varying phenotypic response of different cell lines to Salmonella infection. These findings have implications for the interpretation and reproducibility of research results obtained from human cultured cells. Overall design: Multi-omic (genome, transcriptome, proteome, protein turnover) analysis of 14 HeLa cell lines obtained from different laboratories but grown under the same conditions.
Multi-omic measurements of heterogeneity in HeLa cells across laboratories.
Specimen part, Subject
View SamplesWe used microarrays to detail the global changes in gene expression resulting from miR-95 overexpression
miRNA-95 mediates radioresistance in tumors by targeting the sphingolipid phosphatase SGPP1.
Cell line, Treatment
View SamplesAvian coccidiosis is a major disease of poultry caused by the intestinal protozoa Eimeria. Aviagen line A and line B birds show differential susceptibility to Eimeria infection, with line B birds exhibiting higher lesion scores and mortality. The objective of this study was to examine differential intestinal gene expression between line A and B chicks in response to a challenge with Eimeria maxima. Following challenge with 1 x 10^4 oocysts/chick, greater than 40% of line A chicks had lesion scores of 0 to 1 (on 0 to 4 scale), similar to controls. In contrast, all line B challenged chicks at this same dose had lesion scores of 2 to 4.
An antimicrobial peptide is downregulated in the small intestine of Eimeria maxima-infected chickens.
Specimen part
View SamplesBy using high-density DNA microarrays, we analyzed the gene-expression profile of SHSY5Y neuroblastoma cells after treatment with cobalt chloride
Investigation of Endogenous Retrovirus Sequences in the Neighborhood of Genes Up-regulated in a Neuroblastoma Model after Treatment with Hypoxia-Mimetic Cobalt Chloride.
Specimen part, Cell line
View SamplesWe microdissected discrete sub-regions of esophageal squamous cell carcinoma (ESCC) and analyzed the transcriptomes throughout three-dimensional (3D) tumor space.
Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma.
Specimen part, Disease
View SamplesWe utilized tissue microdissection and expression microarrays to measure ex vivo gene expression profiles in twelve cases of patient-matched normal basal epithelial cells, normal differentiated squamous epithelium, and cancer.
Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma.
Specimen part, Disease
View SamplesMS-275 and hydroxyurea treatment influences whole gene expression including DNA damage response and cell cycle checkpoint signaling.
HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.
Specimen part, Time
View SamplesCircadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erb , a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes. Here we show that Rev-erb modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erb to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erb regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erb and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erb utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue.
GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.
Specimen part, Time
View SamplesTo investigate the role of viral and host factors in HDV-associated HCC we carried out an integrated clinicopathological and gene expression study of tissue specimens and laser microdissected hepatocytes obtained at the time of liver transplantation from livers with HDV-HCC, HDV-cirrhosis without HCC, HCV-HCC and HBV-HCC. References to GSM series of HDV and HBV livers, already deposited in GEO, are included in this series. Part of data of HCV livers are a re-analysis of GSE series GSE69715 and GSE78737, the re-analyzed GSM is indicated in the 'description' column and with a link at the bottom of the page.
Molecular Signature and Mechanisms of Hepatitis D Virus-Associated Hepatocellular Carcinoma.
Sex, Specimen part, Disease, Disease stage, Subject
View Samples