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Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells

Human bone marrow-mesenchymal stromal cells (hBM-MSCs) undergo cellular senescence during in vitro culture. In this study, we defined this replicative senescence as impaired proliferation, deterioration in representative cell characteristics, accumulated DNA damage, and decreased telomere length and...

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Autores principales: Kim, Jiyeon, Kim, Yonggoo, Choi, Hayoung, Kwon, Ahlm, Jekarl, Dong Wook, Lee, Seungok, Jang, Woori, Chae, Hyojin, Kim, Jung Rok, Kim, Jung Min, Kim, Myungshin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833785/
https://www.ncbi.nlm.nih.gov/pubmed/29382826
http://dx.doi.org/10.1038/s41419-017-0032-5
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author Kim, Jiyeon
Kim, Yonggoo
Choi, Hayoung
Kwon, Ahlm
Jekarl, Dong Wook
Lee, Seungok
Jang, Woori
Chae, Hyojin
Kim, Jung Rok
Kim, Jung Min
Kim, Myungshin
author_facet Kim, Jiyeon
Kim, Yonggoo
Choi, Hayoung
Kwon, Ahlm
Jekarl, Dong Wook
Lee, Seungok
Jang, Woori
Chae, Hyojin
Kim, Jung Rok
Kim, Jung Min
Kim, Myungshin
author_sort Kim, Jiyeon
collection PubMed
description Human bone marrow-mesenchymal stromal cells (hBM-MSCs) undergo cellular senescence during in vitro culture. In this study, we defined this replicative senescence as impaired proliferation, deterioration in representative cell characteristics, accumulated DNA damage, and decreased telomere length and telomerase activity with or without genomic abnormalities. The UBC gene expression gradually decreased during passaging along with the reduction in series of molecules including hub genes; CDK1, CCNA2, MCM10, E2F1, BRCA1, HIST1H1A and HIST1H3B. UBC knockdown in hBM-MSCs induced impaired proliferation in dose-dependent manner and showed replicative senescence-like phenomenon. Gene expression changes after UBC knockdown were similar to late passage hBM-MSCs. Additionally, UBC overexpession improved the proliferation activity of hBM-MSCs accompanied by increased expression of the hub genes. Consequently, UBC worked in higher-order through regulation of the hub genes controlling cell cycle and proliferation. These results indicate that the decrement of UBC expression plays a pivotal role in replicative senescence of hBM-MSCs.
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spelling pubmed-58337852018-03-06 Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells Kim, Jiyeon Kim, Yonggoo Choi, Hayoung Kwon, Ahlm Jekarl, Dong Wook Lee, Seungok Jang, Woori Chae, Hyojin Kim, Jung Rok Kim, Jung Min Kim, Myungshin Cell Death Dis Article Human bone marrow-mesenchymal stromal cells (hBM-MSCs) undergo cellular senescence during in vitro culture. In this study, we defined this replicative senescence as impaired proliferation, deterioration in representative cell characteristics, accumulated DNA damage, and decreased telomere length and telomerase activity with or without genomic abnormalities. The UBC gene expression gradually decreased during passaging along with the reduction in series of molecules including hub genes; CDK1, CCNA2, MCM10, E2F1, BRCA1, HIST1H1A and HIST1H3B. UBC knockdown in hBM-MSCs induced impaired proliferation in dose-dependent manner and showed replicative senescence-like phenomenon. Gene expression changes after UBC knockdown were similar to late passage hBM-MSCs. Additionally, UBC overexpession improved the proliferation activity of hBM-MSCs accompanied by increased expression of the hub genes. Consequently, UBC worked in higher-order through regulation of the hub genes controlling cell cycle and proliferation. These results indicate that the decrement of UBC expression plays a pivotal role in replicative senescence of hBM-MSCs. Nature Publishing Group UK 2018-01-30 /pmc/articles/PMC5833785/ /pubmed/29382826 http://dx.doi.org/10.1038/s41419-017-0032-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Jiyeon
Kim, Yonggoo
Choi, Hayoung
Kwon, Ahlm
Jekarl, Dong Wook
Lee, Seungok
Jang, Woori
Chae, Hyojin
Kim, Jung Rok
Kim, Jung Min
Kim, Myungshin
Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells
title Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells
title_full Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells
title_fullStr Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells
title_full_unstemmed Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells
title_short Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells
title_sort ubiquitin c decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833785/
https://www.ncbi.nlm.nih.gov/pubmed/29382826
http://dx.doi.org/10.1038/s41419-017-0032-5
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