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Skeletal muscle characteristics are preserved in hTERT/cdk4 human myogenic cell lines

Thorley, M; Duguez, S; Mazza, EMC; Valsoni, S; Bigot, A; Mamchaoui, K; Harmon, B; ... Duddy, W; + view all (2016) Skeletal muscle characteristics are preserved in hTERT/cdk4 human myogenic cell lines. Skeletal Muscle , 6 (1) , Article 43. 10.1186/s13395-016-0115-5. Green open access

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Abstract

BACKGROUND: 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 genetic modification related to the cell cycle results in secondary effects that could undermine the validity of these cell models. RESULTS: Here we subjected five healthy and disease muscle cell isolates to 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. Principal component analysis of global gene expression showed tight clustering of immortalized myoblasts to their parent primary populations, with clean separation from the non-myogenic reference. Comparison was made to publicly available transcriptomic data from studies of muscle human pathology, cell, and animal models, including to derive a consensus set of genes previously shown to have altered regulation during myoblast differentiation. Hierarchical clustering of samples based on gene expression of this consensus set showed that immortalized lines retained the myogenic expression patterns of their parent primary populations. Of 2784 canonical pathways and gene ontology terms tested by gene set enrichment analysis, none were significantly enriched in immortalized compared to primary cell populations. We observed, at the whole transcriptome level, a strong signature of cell cycle shutdown associated with senescence in one primary myoblast population, whereas its immortalized clone was protected. CONCLUSIONS: Immortalization had no observed effect on the myogenic cascade or on any other cellular processes, and it was protective against the systems level effects of senescence that are observed at higher division counts of primary cells.

Type: Article
Title: Skeletal muscle characteristics are preserved in hTERT/cdk4 human myogenic cell lines
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13395-016-0115-5
Publisher version: http://dx.doi.org/10.1186/s13395-016-0115-5
Language: English
Additional information: © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Cell Line, Cells, Cultured, Cellular Senescence, Cyclin-Dependent Kinase 4, Humans, Muscle Development, Myoblasts, Telomerase, Transcriptome
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10092255
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