title: Epigenetic memory gained by priming with osteogenic induction medium improves osteogenesis and other properties of mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are highly plastic cells that are able to transdifferentiate or dedifferentiate under appropriate conditions. In the present study, we reported here that after in vitro induction of osteogenic differentiation, MSCs could be reverted to a primitive stem cell population (dedifferentiated osteogenic MSCs, De-Os-MSCs) with improved cell survival, colony formation, osteogenic potential, migratory capacity and increased expression of Nanog, Oct4 and Sox2. Most importantly, our results showed great superiority of the De-Os-MSCs over untreated MSCs in ectopic bone formation in vivo. Furthermore, Nanog-knockdown in MSCs could reverse these enhanced properties in De-Os-MSCs in vitro, indicating a central role of Nanog in the transcriptional network. In addition, epigenetic regulations including DNA methylation and histone modifications may play important roles in regulating the de-osteogenic differentiation process. And we found decreased methylation and promoter accrual of activating histone marks, such as H3K4me3 and H4ac on both Nanog and Oct4 gene promoters. Taken together, our study demonstrated that epigenetic memory in De-Os-MSCs gained by priming with osteogenic induction medium favored their differentiation along osteoblastic lineage with improved cell survival and migratory abilities, which may have application potential in enhancing their regenerative capacity in mammals.
authors.affiliation: 1] Department of Orthopaedics, Zhongda Hospital, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, PR China [2] Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, PR China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Rui
authors.affiliation: Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, PR China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Zhongda Hospital, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, PR China.
authors.forename: Sien
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, PR China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Orthopaedics, Zhongda Hospital, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Zhongda Hospital, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, PR China.
authors.forename: Fanbiao
authors.initials: F
authors.lastname: Meng
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 1] Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, PR China [2] The Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ni
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Kam Sze
authors.initials: KS
authors.lastname: Tsang
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Fuyuan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Zhongda Hospital, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China [2] Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China [3] Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China [4] The Chinese University of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
authors.affiliation: 1] Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China [2] Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China [3] Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China [4] The Chinese University of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: 1] Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, PR China [2] Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China [3] Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China [4] Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China [5] The Chinese University of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology; D054337:Cell Dedifferentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics*; D010012:Osteogenesis / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000071317:Nanog Homeobox Protein; C547030:Nanog protein, rat; D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; C527784:Sox2 protein, rat; D014157:Transcription Factors