Premium
Role of histone deacetylase inhibitors in the aging of human umbilical cord mesenchymal stem cells
Author(s) -
Wang Yunshuai,
Chen Tao,
Yan Hongjie,
Qi Hui,
Deng Chunyan,
Ye Tao,
Zhou Shuyan,
Li FuRong
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24569
Subject(s) - histone deacetylase , mesenchymal stem cell , homeobox protein nanog , trichostatin a , microbiology and biotechnology , epigenetics , histone deacetylase 5 , epigenetic regulation of neurogenesis , biology , cancer research , chemistry , histone , induced pluripotent stem cell , histone methyltransferase , embryonic stem cell , biochemistry , gene
Mesenchymal stem cells (MSCs) are self‐renewing cells that exhibit differentiation capacity and immune regulation ability. These versatile cells have a wide range of potential applications. However, the spontaneous differentiation and aging of MSCs during long‐term culturing restrict the amount of cells available for therapies and tissue engineering. Thus, maintaining the biological characteristics of MSCs during long‐term culturing is crucial. Chromatic modification via epigenetic regulatory mechanisms (e.g., histone acetylation, deacetylation, and methylation) is crucial in stem cell pluripotency. We investigated the effects of largazole or trichostatin A (TSA), a novel histone deacetylase inhibitor (HDACi), against human umbilical cord (hUC)‐MSCs aging. Results show that low concentrations of largazole or TSA can significantly improve hUC‐MSCs proliferation and delay hUC‐MSCs aging. Largazole can better improve MSCs proliferation than TSA. HDAC is modulate histone H3 acetylation and methylation in the telomerase reverse‐transcriptase, octamer‐binding transcription factor 4, Nanog, C‐X‐C chemokine receptor 4, alkaline phosphatase, and osteopontin genes. HDACis can promote hUC‐MSCs proliferation and suppress hUC‐MSCs spontaneous osteogenic differentiation. HDACis can affect histone H3 lysine 9 or 14 acetylation and histone H3 lysine 4 dimethylation, thus increasing the mRNA expression of pluripotent and proliferative genes and suppressing the spontaneous differentiation of hUC‐MSCs. J. Cell. Biochem. 114: 2231–2239, 2013. © 2013 Wiley Periodicals, Inc.