The transcriptome of wild-type and immortalized corneal epithelial cells

Furuya, Kai; Wu, Tao; Orimoto, Ai; Sugano, Eriko; Tomita, Hiroshi; Kiyono, Tohru; Kurose, Takahiro; Takai, Yoshihiro; Fukuda, T.

doi:10.1038/s41597-021-00908-9

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…2B in their paper). Based on a previous study that reported genes that were significantly differentially expressed upon induction of the Large T-antigen (Furuya et al, 2021), we noted that more than half of the signature genes compiled for iOSNs, as well as other cell types from the olfactory epithelium (OE), were significantly impacted. The fact that immortalized OP6 cells nevertheless reliably exhibit phenotypic attributes of an iOSN suggests a robust system of post-transcriptional regulation to stabilize cell identity.…”

Section: Resultsmentioning

confidence: 99%

“…We trimmed genes previously shown to be misregulated with Large T-antigen expression (Furuya et al, 2021) from the ranked set of signature genes in each of six different OE cell types (Zunitch et al, 2023). We scored OP6 cells based on the normalized FPKM expression level for the top 250 signature genes in each list weighted for relevance based on their ranked position (see Methods).…”

Section: Resultsmentioning

confidence: 99%

“…Despite these affirming phenotypic traits, the OP cell lines have not previously been characterized at the transcriptome level, where we anticipated that immortalization by the Large T-antigen would likely impose a large global impact on RNA expression profiles (Furuya et al, 2021). Here, we analyzed the bulk transcriptome of OP6 cell populations to gain further insights into the developmental status of this cell line.…”

Section: Resultsmentioning

confidence: 99%

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Transformation of an olfactory placode-derived cell into one with stem cell characteristics by disrupting epigenetic barriers

Abbas,

Vyas,

Noble

et al. 2024

Preprint

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The mammalian olfactory neuronal lineage is regenerative, and accordingly, maintains a population of pluripotent cells that replenish olfactory sensory neurons and other olfactory cell types during the life of the animal. Moreover, in response to acute injury, the early transit amplifying cells along the olfactory sensory neuronal lineage are able to de-differentiate to shift resources in support of tissue restoration. In order to further explore plasticity of various cellular stages along the olfactory sensory neuronal lineage, we challenged the epigenetic stability of two olfactory placode-derived cell lines that model immature olfactory sensory neuronal stages. We found that perturbation of the Ehmt2 chromatin modifier transformed the growth properties, morphology, and gene expression profiles towards states with several stem cell characteristics. This transformation was dependent on continued expression of the large T-antigen, and was enhanced by Sox2 over-expression. These findings may provide momentum for exploring inherent cellular plasticity within early cell types of the olfactory lineage, as well as potentially add to our knowledge of cellular reprogramming.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Transformation of an olfactory placode-derived cell into one with stem cell characteristics by disrupting epigenetic barriers

Abbas,

Vyas,

Noble

et al. 2024

Preprint

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“…3D corneal epithelial permeation model using immortalized human primary corneal epithelial cells (HCE-T cells): (A) Morphologies of wild-type, K4DT, and SV40 immortalized corneal epithelial cells. Reprinted from ref with permission under a Creative Commons License 4.0. Copyright 2021 Springer Nature.…”

Section: In Vitro Reconstructed Corneal Tissue Models To Study Drug P...mentioning

confidence: 99%

In Vitro and Ex Vivo Models for Assessing Drug Permeation across the Cornea

et al. 2023

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Drug permeation across the cornea remains a major challenge due to its unique and complex anatomy and physiology. Static barriers such as the different layers of the cornea, as well as dynamic aspects such as the constant renewal of the tear film and the presence of the mucin layer together with efflux pumps, all present unique challenges for effective ophthalmic drug delivery. To overcome some of the current ophthalmic drug limitations, the identification and testing of novel drug formulations such as liposomes, nanoemulsions, and nanoparticles began to be considered and widely explored. In the early stages of corneal drug development reliable in vitro and ex vivo alternatives, are required, to be in line with the principles of the 3Rs (Replacement, Reduction, and Refinement), with such methods being in addition faster and more ethical alternatives to in vivo studies. The ocular field remains limited to a handful of predictive models for ophthalmic drug permeation. In vitro cell culture models are increasingly used when it comes to transcorneal permeation studies. Ex vivo models using excised animal tissue such as porcine eyes are the model of choice to study corneal permeation and promising advancements have been reported over the years. Interspecies characteristics must be considered in detail when using such models. This review updates the current knowledge about in vitro and ex vivo corneal permeability models and evaluates their advantages and limitations.

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“…Thus, it is necessary to find a replacement for SV40T to use in tandem with hTERT. BMI-1 [27,35,37,145,158], cyclin D1, and CDK4R24C (mutant cyclin-dependent kinase 4, which cannot be bound by p16INK4a) [159][160][161][162] can be used for this purpose. Studies have demonstrated that hTERT in combination with BMI-1 as immortogenes are associated with the lowest level of chromosome aberrations among SV40T-, hTERT-, and hTERT-BMI-1-immortalized cells [145].…”

mentioning

confidence: 99%

Immortalization Reversibility in the Context of Cell Therapy Biosafety

Sutyagina

Beilin

Vorotelyak

et al. 2023

IJMS

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Immortalization (genetically induced prevention of replicative senescence) is a promising approach to obtain cellular material for cell therapy or for bio-artificial organs aimed at overcoming the problem of donor material shortage. Immortalization is reversed before cells are used in vivo to allow cell differentiation into the mature phenotype and avoid tumorigenic effects of unlimited cell proliferation. However, there is no certainty that the process of de-immortalization is 100% effective and that it does not cause unwanted changes in the cell. In this review, we discuss various approaches to reversible immortalization, emphasizing their advantages and disadvantages in terms of biosafety. We describe the most promising approaches in improving the biosafety of reversibly immortalized cells: CRISPR/Cas9-mediated immortogene insertion, tamoxifen-mediated self-recombination, tools for selection of successfully immortalized cells, using a decellularized extracellular matrix, and ensuring post-transplant safety with the use of suicide genes. The last process may be used as an add-on for previously existing reversible immortalized cell lines.

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The transcriptome of wild-type and immortalized corneal epithelial cells

Cited by 6 publications

References 19 publications

Transformation of an olfactory placode-derived cell into one with stem cell characteristics by disrupting epigenetic barriers

Transformation of an olfactory placode-derived cell into one with stem cell characteristics by disrupting epigenetic barriers

In Vitro and Ex Vivo Models for Assessing Drug Permeation across the Cornea

Immortalization Reversibility in the Context of Cell Therapy Biosafety

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