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lncRNA H19 facilitates the proliferation and differentiation of human dental pulp stem cells via EZH2-dependent LATS1 methylation

Human dental pulp stem cells (hDPSCs) have been recognized as a candidate cell source for tissue engineering. Long non-coding RNAs (lncRNAs) are differentially expressed in inflamed human dental pulp tissues. The present study is aimed at investigating the role of lncRNA H19 in the differentiation p...

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Detalles Bibliográficos
Autores principales: Du, Zhen, Shi, Xiaoming, Guan, Aizhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339349/
https://www.ncbi.nlm.nih.gov/pubmed/34401209
http://dx.doi.org/10.1016/j.omtn.2021.04.017
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author Du, Zhen
Shi, Xiaoming
Guan, Aizhong
author_facet Du, Zhen
Shi, Xiaoming
Guan, Aizhong
author_sort Du, Zhen
collection PubMed
description Human dental pulp stem cells (hDPSCs) have been recognized as a candidate cell source for tissue engineering. Long non-coding RNAs (lncRNAs) are differentially expressed in inflamed human dental pulp tissues. The present study is aimed at investigating the role of lncRNA H19 in the differentiation potential of hDPSCs. hDPSCs were successfully isolated and cultured, followed by conducting gain and loss-of-function experiments on lncRNA H19 and large tumor suppressor 1 (LATS1) to elucidate their respective biological functions in hDPSCs. lncRNA H19 was able to promote, whereas LATS1 was found to inhibit the differentiation, proliferation, and migration capabilities of hDPSCs. LATS1 was found to activate the Hippo-Yes-associated protein (YAP) signaling pathway by decreasing levels of YAP and Tafazzin (TAZ). The effects of lncRNA H19 on hDPSCs were achieved by repressing LATS1 through enhancer of zeste homolog 2-induced trimethylation of histone 3 at lysine 27. Finally, hDPSCs overexpressing lncRNA H19 and/or LATS1 were transplanted into nude mice. It was shown that lncRNA H19 inhibited LATS1 to promote the production of odontoblasts in vivo. Taken together, lncRNA H19 serves as a contributor to the differentiation potential of hDPSCs via the inhibition of LATS1, therefore highlighting novel therapeutic targets for dental pulp repair.
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spelling pubmed-83393492021-08-15 lncRNA H19 facilitates the proliferation and differentiation of human dental pulp stem cells via EZH2-dependent LATS1 methylation Du, Zhen Shi, Xiaoming Guan, Aizhong Mol Ther Nucleic Acids Original Article Human dental pulp stem cells (hDPSCs) have been recognized as a candidate cell source for tissue engineering. Long non-coding RNAs (lncRNAs) are differentially expressed in inflamed human dental pulp tissues. The present study is aimed at investigating the role of lncRNA H19 in the differentiation potential of hDPSCs. hDPSCs were successfully isolated and cultured, followed by conducting gain and loss-of-function experiments on lncRNA H19 and large tumor suppressor 1 (LATS1) to elucidate their respective biological functions in hDPSCs. lncRNA H19 was able to promote, whereas LATS1 was found to inhibit the differentiation, proliferation, and migration capabilities of hDPSCs. LATS1 was found to activate the Hippo-Yes-associated protein (YAP) signaling pathway by decreasing levels of YAP and Tafazzin (TAZ). The effects of lncRNA H19 on hDPSCs were achieved by repressing LATS1 through enhancer of zeste homolog 2-induced trimethylation of histone 3 at lysine 27. Finally, hDPSCs overexpressing lncRNA H19 and/or LATS1 were transplanted into nude mice. It was shown that lncRNA H19 inhibited LATS1 to promote the production of odontoblasts in vivo. Taken together, lncRNA H19 serves as a contributor to the differentiation potential of hDPSCs via the inhibition of LATS1, therefore highlighting novel therapeutic targets for dental pulp repair. American Society of Gene & Cell Therapy 2021-04-24 /pmc/articles/PMC8339349/ /pubmed/34401209 http://dx.doi.org/10.1016/j.omtn.2021.04.017 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Du, Zhen
Shi, Xiaoming
Guan, Aizhong
lncRNA H19 facilitates the proliferation and differentiation of human dental pulp stem cells via EZH2-dependent LATS1 methylation
title lncRNA H19 facilitates the proliferation and differentiation of human dental pulp stem cells via EZH2-dependent LATS1 methylation
title_full lncRNA H19 facilitates the proliferation and differentiation of human dental pulp stem cells via EZH2-dependent LATS1 methylation
title_fullStr lncRNA H19 facilitates the proliferation and differentiation of human dental pulp stem cells via EZH2-dependent LATS1 methylation
title_full_unstemmed lncRNA H19 facilitates the proliferation and differentiation of human dental pulp stem cells via EZH2-dependent LATS1 methylation
title_short lncRNA H19 facilitates the proliferation and differentiation of human dental pulp stem cells via EZH2-dependent LATS1 methylation
title_sort lncrna h19 facilitates the proliferation and differentiation of human dental pulp stem cells via ezh2-dependent lats1 methylation
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339349/
https://www.ncbi.nlm.nih.gov/pubmed/34401209
http://dx.doi.org/10.1016/j.omtn.2021.04.017
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