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      Combinatorial expression of cell cycle regulators is more suitable for immortalization than oncogenic methods in dermal papilla cells

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          Summary

          The immortalized cell is an essential research tool that uses robust growth properties for the functional investigation of gene products. Immortalized mammalian cells have mainly been established using three methods: expression of simian vacuolating virus 40 T antigen (the SV40 method); human papilloma virus-derived oncoprotein E6/E7 (the E6/E7 method); or combinatorial expression of R24C mutant cyclin-dependent kinase 4, cyclin D1, and telomerase reverse transcriptase (the K4DT method). However, it is unclear as to which method is optimal for an in vitro model. Here, we compared the biological characteristics and genome-wide expression profiles of immortalized human dermal papilla cells generated by the SV40, E6/E7, or K4DT method. To our knowledge, this is the first study to comprehensively compare expression profiles to determine the optimal immortalization method for maintaining the original nature of the wild-type cells. These data would be valuable to scientists aiming to establish new immortalized cell lines.

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          Highlights

          • Expression profiles of immortalized dermal papilla cells by the SV40, E6/E7, K4DT method were analyzed

          • The distance from wild type to K4DT was close, E6E7 was middle, SV40 was most distant

          • K4DT method showed the most conservative profile when it compared with SV40 and E6E7 method

          Abstract

          Cell Biology; Stem Cell Research; Technical Aspects of Cell Biology

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          Most cited references25

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          Cancer. p53, guardian of the genome.

          D P Lane (1992)
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            Exosomes: biogenesis, biologic function and clinical potential

            Exosomes are nano-sized biovesicles released into surrounding body fluids upon fusion of multivesicular bodies and the plasma membrane. They were shown to carry cell-specific cargos of proteins, lipids, and genetic materials, and can be selectively taken up by neighboring or distant cells far from their release, reprogramming the recipient cells upon their bioactive compounds. Therefore, the regulated formation of exosomes, specific makeup of their cargo, cell-targeting specificity are of immense biological interest considering extremely high potential of exosomes as non-invasive diagnostic biomarkers, as well as therapeutic nanocarriers. In present review, we outline and discuss recent progress in the elucidation of the regulatory mechanisms of exosome biogenesis, the molecular composition of exosomes, and technologies used in exosome research. Furthermore, we focus on the potential use of exosomes as valuable diagnostic and prognostic biomarkers for their cell-lineage and state-specific contents, and possibilities as therapeutic vehicles for drug and gene delivery. Exosome research is now in its infancy, in-depth understanding of subcellular components and mechanisms involved in exosome formation and specific cell-targeting will bring light on their physiological activities.
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              THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS.

              L Hayflick (1965)
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                Author and article information

                Contributors
                Journal
                iScience
                iScience
                iScience
                Elsevier
                2589-0042
                11 December 2020
                22 January 2021
                11 December 2020
                : 24
                : 1
                : 101929
                Affiliations
                [1 ]Graduate School of Science and Engineering, Iwate University, 4-3-5 Ueda, Morioka, Iwate, 020-8551 Japan
                [2 ]Rohto Pharmaceutical Co., Ltd., Basic Research Development Division, 6-5-4 Kunimidai, Kizugawa, Kyoto, 619-0216, Japan
                [3 ]Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa-city, Chiba, 277-8577, Japan
                Author notes
                []Corresponding author tomofukuda009@ 123456gmail.com
                [∗∗ ]Corresponding author tkiyono@ 123456ncc.go.jp
                [∗∗∗ ]Corresponding author ishii@ 123456rohto.co.jp
                [4]

                Lead contact

                Article
                S2589-0042(20)31126-3 101929
                10.1016/j.isci.2020.101929
                7788094
                33437932
                a0667635-7149-4840-beae-a9d19a9966ed
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 29 May 2020
                : 5 November 2020
                : 8 December 2020
                Categories
                Article

                cell biology,stem cell research,technical aspects of cell biology

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