title: Role of histone deacetylase inhibitors in the aging of human umbilical cord mesenchymal stem cells.
abstract: 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.
authors.affiliation: Department of General Surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
authors.forename: Yunshuai
authors.initials: Y
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yan
authors.forename: Hui
authors.initials: H
authors.lastname: Qi
authors.forename: Chunyan
authors.initials: C
authors.lastname: Deng
authors.forename: Tao
authors.initials: T
authors.lastname: Ye
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zhou
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D047369:Chromatin Immunoprecipitation; D047630:Depsipeptides / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013844:Thiazoles; C527895:largazole; C012589:trichostatin A
keywords: EPIGENETIC MODIFICATION; HISTONE DEACETYLASE INHIBITOR; HUMAN UMBILICAL CORD-MESENCHYMAL STEM CELL; PROLIFERATION