hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically-pertinent models of various neuromuscular disorders and in numerous fundamental studies of muscle cell function. However, the cell cycle is linked to other cellular processes such as integrin regulation, the PI3K/Akt pathway, and microtubule stability, raising the question as to whether transgenic modification of the cell cycle results in secondary effects that could undermine the validity of these cell models. Here we subjected healthy and disease lines to intensive transcriptomic analysis, comparing immortalized lines with their parent primary populations in both differentiated and undifferentiated states, and testing their myogenic character by comparison with non-myogenic (CD56-negative) cells. We found that immortalization has no measurable effect on the myogenic cascade or on any other cellular processes, and that it was protective against the systems level effects of senescence that are observed at higher division counts of primary cells.
Skeletal muscle characteristics are preserved in hTERT/cdk4 human myogenic cell lines.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sex, Specimen part, Time
View SamplesDNA methylation plays a vital role in the cell, but loss-of-function mutations of the maintenance methyltransferase DNMT1 in normal human cells are lethal, precluding target identification, and existing hypomorphic lines are tumour cells. We generated instead a hypomorphic series in normal hTERT-immortalised fibroblasts using stably integrated short hairpin RNA. Approx 2/3 of sites showed demethylation as expected, with 1/3 showing hypermethylation, and targets were shared between the three independently-derived lines. Enrichment analysis indicated significant losses at promoters and gene bodies with four gene classes most affected: 1)protocadherins, which are key to neural cell identity; 2)genes involved in fat homeostasis/body mass determination; 3)olfactory receptors and 4) cancer/testis antigen (CTA) genes. Overall effects on transcription were relatively small in these fibroblasts, but CTA genes showed robust derepression. Comparison with siRNA-treated cells indicated that shRNA lines show substantial remethylation over time. Regions showing persistent hypomethylation in the shRNA lines were associated with polycomb repression, and were derepressed on addition of an EZH2 inhibitor. Persistent hypermethylation in shRNA lines was in contrast associated with poised promoters. Our results suggest polycomb marking blocks remethylation and indicate the sensitivity of key neural, adipose, and cancer-associated genes to chronic depletion of maintenance methylation activity.
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sex, Specimen part, Time
View SamplesFrom the parental breast cancer cell line MCF7 (weakly invasive), we progressively selected hyperinvasive subclones. We compared the gene expression between the parental MCF7-I0 and the hyper-invasive cells MCF7-I6.
No associated publication
Specimen part, Cell line
View SamplesThe purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesGene expression profile comparison from fibroblasts of Huntington individuals and normal ones
Gene expression profile in fibroblasts of Huntington's disease patients and controls.
Sex, Age, Specimen part, Disease
View SamplesComparison of the differential expression mRNA profiles from the brain cortex of hypoxia and normaixa rats by silica microarray chip
No associated publication
Specimen part
View SamplesBone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats
Identification of genes influencing skeletal phenotypes in congenic P/NP rats.
No sample metadata fields
View SamplesFemoral neck bone mineral density and structure candidate gene analysis in Fischer 344 (F344) and Lewis (LEW) rats
Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck.
No sample metadata fields
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