<P>Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-deri...
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https://www.riss.kr/link?id=A107566806
2011
-
SCI,SCIE,SCOPUS
학술저널
325-336(12쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P>Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-deri...
<P>Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) caused by inhibition of histone deacetylase (HDAC) activity leads to down-regulation of high mobility group A2 (HMGA2) and, on the contrary, to up-regulation of p16<SUP>INK4A</SUP>, p21<SUP>CIP1/WAF1</SUP> and p27<SUP>KIP1</SUP>. We found that let-7a1, let-7d, let-7f1, miR-23a, miR-26a and miR-30a were increased during replicative and HDAC inhibitor-mediated senescence of hUCB-MSCs by microRNA microarray and real-time quantitative PCR. Furthermore, the configurations of chromatins beading on these miRNAs were prone to transcriptional activation during HDAC inhibitor-mediated senescence. We confirmed that miR-23a, miR-26a and miR-30a inhibit HMGA2 to accelerate the progress of senescence. These findings suggest that HDACs may play important roles in cellular senescence by regulating the expression of miRNAs that target HMGA2 through histone modification.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00018-010-0457-9) contains supplementary material, which is available to authorized users.</P>