Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents

Abstract The DNA demethylating agent, 5-Azacytidine (5Aza), and histone deacetylase inhibitor, valproic acid (Vpa), can improve the reprogramming efficiencies of pluripotent cells. This study aimed to examine the roles of 5Aza and Vpa in the dedifferentiation of epithelial cell rests of Malassez (ER...

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Autores principales: Koki Yoshida, Osamu Uehara, Yoshihito Kurashige, Durga Paudel, Aya Onishi, Puja Neopane, Daichi Hiraki, Tetsuro Morikawa, Fumiya Harada, Rie Takai, Jun Sato, Masato Saitoh, Yoshihiro Abiko
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:d84d9fdd546a47f8b5875b4315730b1b2021-12-02T10:49:11ZDirect reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents10.1038/s41598-020-79426-42045-2322https://doaj.org/article/d84d9fdd546a47f8b5875b4315730b1b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79426-4https://doaj.org/toc/2045-2322Abstract The DNA demethylating agent, 5-Azacytidine (5Aza), and histone deacetylase inhibitor, valproic acid (Vpa), can improve the reprogramming efficiencies of pluripotent cells. This study aimed to examine the roles of 5Aza and Vpa in the dedifferentiation of epithelial cell rests of Malassez (ERM) into stem-like cells. Additionally, the ability of stem-like cells to differentiate into mesenchymal cells was evaluated. ERM was cultured in embryonic stem cell medium (ESCM) with 1 µM of 5Aza, or 2 mM of Vpa, or a combination of 5Aza and Vpa. The cells stimulated with both 5Aza and Vpa were named as progenitor-dedifferentiated into stem-like cells (Pro-DSLCs). The Pro-DSLCs cultured in ESCM alone for another week were named as DSLCs. The stem cell markers were significantly higher in the DSLCs than the controls (no additions). The mRNA and protein levels of the endothelial, mesenchymal stem, and osteogenic cell markers were significantly higher in the Pro-DSLCs and DSLCs than the controls. The combination of a demethylating agent and a deacetylated inhibitor induced the dedifferentiation of ERM into DSLCs. The Pro-DSLCs derived from ERM can be directly reprogrammed into mesenchymal-like cells without dedifferentiation into stem-like cells. Isolated ERM treated with epigenetic agents may be used for periodontal regeneration.Koki YoshidaOsamu UeharaYoshihito KurashigeDurga PaudelAya OnishiPuja NeopaneDaichi HirakiTetsuro MorikawaFumiya HaradaRie TakaiJun SatoMasato SaitohYoshihiro AbikoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Koki Yoshida
Osamu Uehara
Yoshihito Kurashige
Durga Paudel
Aya Onishi
Puja Neopane
Daichi Hiraki
Tetsuro Morikawa
Fumiya Harada
Rie Takai
Jun Sato
Masato Saitoh
Yoshihiro Abiko
Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents
description Abstract The DNA demethylating agent, 5-Azacytidine (5Aza), and histone deacetylase inhibitor, valproic acid (Vpa), can improve the reprogramming efficiencies of pluripotent cells. This study aimed to examine the roles of 5Aza and Vpa in the dedifferentiation of epithelial cell rests of Malassez (ERM) into stem-like cells. Additionally, the ability of stem-like cells to differentiate into mesenchymal cells was evaluated. ERM was cultured in embryonic stem cell medium (ESCM) with 1 µM of 5Aza, or 2 mM of Vpa, or a combination of 5Aza and Vpa. The cells stimulated with both 5Aza and Vpa were named as progenitor-dedifferentiated into stem-like cells (Pro-DSLCs). The Pro-DSLCs cultured in ESCM alone for another week were named as DSLCs. The stem cell markers were significantly higher in the DSLCs than the controls (no additions). The mRNA and protein levels of the endothelial, mesenchymal stem, and osteogenic cell markers were significantly higher in the Pro-DSLCs and DSLCs than the controls. The combination of a demethylating agent and a deacetylated inhibitor induced the dedifferentiation of ERM into DSLCs. The Pro-DSLCs derived from ERM can be directly reprogrammed into mesenchymal-like cells without dedifferentiation into stem-like cells. Isolated ERM treated with epigenetic agents may be used for periodontal regeneration.
format article
author Koki Yoshida
Osamu Uehara
Yoshihito Kurashige
Durga Paudel
Aya Onishi
Puja Neopane
Daichi Hiraki
Tetsuro Morikawa
Fumiya Harada
Rie Takai
Jun Sato
Masato Saitoh
Yoshihiro Abiko
author_facet Koki Yoshida
Osamu Uehara
Yoshihito Kurashige
Durga Paudel
Aya Onishi
Puja Neopane
Daichi Hiraki
Tetsuro Morikawa
Fumiya Harada
Rie Takai
Jun Sato
Masato Saitoh
Yoshihiro Abiko
author_sort Koki Yoshida
title Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents
title_short Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents
title_full Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents
title_fullStr Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents
title_full_unstemmed Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents
title_sort direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/d84d9fdd546a47f8b5875b4315730b1b
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