A transcriptomic analysis of the EK1.Br strain of human fibroblastoid keratocytes: The effects of growth, quiescence and senescence
Abstract
There is a growing need within ocular research for well-defined cellular models of normal corneal biology. To meet this need we created and partially characterised a standard strain of human fibroblastoid keratocytes (EK1.Br) and demonstrated that phenotypic changes occur within these cells with replicative senescence in vitro. Using Affymetrix HG-U133A oligonucleotide arrays, this paper reports both a comprehensive analysis of the transcriptome of EK1.Br in the growing, quiescent and senescent states and a comparison of that transcriptome with those of primary corneal endothelium, lung fibroblasts and dermal fibroblasts grown under identical conditions. Data mining shows (i) that EK1.Br retain the characteristic transcriptional fingerprint of keratocytes in vitro (ii) that this phenotype can be distinguished from those of other 'fibroblasts' by groups of highly differentially expressed genes and (iii) that senescence induces a distinct dedifferentiation phenomenon in EK1.Br. These findings are contextualised into the broader literature on replicative senescence and are supported with a web-accessible and fully searchable public-access database (www.madras.cf.ac.uk/cornea).
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The composition and intensity of the SASP response can be affected by the senescence-inducing mechanism, cell type, and time since senescence initiation, indicating that there is no singular SASP.
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From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [15]
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- Authors
- Kipling, D., Jones, D. L., Smith, S. K., Giles, P. J., Jennert-Burston, K., Ibrahim, B., Sheerin, A. N. P., Evans, A. J. C., Rhys-Willams, W., & Faragher, R. G. A.
- Affiliations
- Cardiff University (GB)
- University of Brighton (GB)
- Corresponding author
- Faragher, Richard G.A.
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 88
- Issue
- 2
- Pages
- 277-285
- ISSN
- 0014-4835 (ISSN-L)
- OpenAlex
- W2001294667
- Cited by
- 18
- References
- 24
- Citations by year
- 2026: 1 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- University of Brighton Repository (University of Brighton) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (EGH16151)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal Surgery and Treatments
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Keywords
- replicative senescence, corneal endothelium, corneal fibroblasts, transcriptome, gene expression profiling, quiescent cells, dedifferentiation, differentially expressed genes
- MeSH terms
- Cell Cycle, Cell Line, Cornea, Humans, Phenotype, Keratinocytes, Cellular Senescence, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic, Cell Proliferation
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