title: Epigenetic changes of mesenchymal stem cells in three-dimensional (3D) spheroids.
abstract: Mesenchymal stem cells (MSCs) hold profound promise in tissue repair/regeneration. However, MSCs undergo remarkable spontaneous differentiation and aging during monolayer culture expansion. In this study, we found that 2-3 days of three-dimensional (3D) spheroid culture of human MSCs (hMSCs) that had been expanded in monolayer for six passages increased their clonogenicity and differentiation potency to neuronal cells. Moreover, in accordance with these changes, the expression levels of miRNA which were involved in stem cell potency were changed and levels of histone H3 acetylation in K9 in promoter regions of Oct4, Sox2 and Nanog were elevated. Our results indicate that spheroid culture increases their multi-potency and changes the epigenetic status of pluripotent genes in hMSCs.
authors.affiliation: The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Yaojiong
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000107:Acetylation; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology* / Q000378:metabolism*
chemical_list: D006657:Histones; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: 3D culture; histone acetylation; mesenchymal stem cells; miRNA; multi-potency
references.citation: IEEE Trans Inf Technol Biomed. 2004 Mar;8(1):36-46
references.pmid: 15055800
references.citation: Stem Cells Int. 2010 Oct 31;2010:503593
references.pmid: 21052537
references.citation: Nat Protoc. 2006;1(1):179-85
references.pmid: 17406230
references.citation: Stem Cells. 2007 Nov;25(11):2739-49
references.pmid: 17656645
references.citation: Cell. 2008 Feb 22;132(4):532-6
references.pmid: 18295569
references.citation: Stem Cells Int. 2011;2011:201371
references.pmid: 21772852
references.citation: Blood. 2007 Aug 15;110(4):1362-9
references.pmid: 17483296
references.citation: Mol Ther. 2012 Jul;20(7):1424-33
references.pmid: 22453767
references.citation: Stem Cells. 2007 Dec;25(12):3143-54
references.pmid: 17761754
references.citation: Cytotherapy. 2006;8(3):194-5
references.pmid: 16793727
references.citation: Exp Hematol. 2011 Jun;39(6):608-16
references.pmid: 21288479
references.citation: Nature. 2012 Feb 23;482(7386):524-8
references.pmid: 22358842
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13724-9
references.pmid: 20643923
references.citation: J Genet Genomics. 2008 Oct;35(10):585-93
references.pmid: 18937915
references.citation: J Biomed Sci. 2010 Jul 29;17:64
references.pmid: 20670406
references.citation: Stem Cells. 2012 Dec;30(12):2746-59
references.pmid: 22949105
references.citation: Biochem Biophys Res Commun. 2001 Mar 23;282(1):148-52
references.pmid: 11263984
references.citation: Science. 1997 Apr 4;276(5309):71-4
references.pmid: 9082988
references.citation: Stem Cell Rev Rep. 2012 Mar;8(1):243-50
references.pmid: 21706142
references.citation: Brain Res. 2011 Jan 7;1367:103-13
references.pmid: 20977892
references.citation: Aging Cell. 2011 Feb;10(1):66-79
references.pmid: 20969724
references.citation: Cell. 2009 May 15;137(4):647-58
references.pmid: 19409607
references.citation: Cell Stem Cell. 2012 Jun 14;10(6):709-716
references.pmid: 22704511
references.citation: Stem Cells Dev. 2008 Aug;17(4):613-8
references.pmid: 18673001
references.citation: Nat Rev Genet. 2005 Aug;6(8):611-22
references.pmid: 16136653
references.citation: Stem Cells. 2007 Oct;25(10):2648-59
references.pmid: 17615264
references.citation: Ageing Res Rev. 2010 Nov;9 Suppl 1:S59-66
references.pmid: 20708718
references.citation: Stem Cells. 2013 Jan;31(1):215-20
references.pmid: 23097343
references.citation: Blood. 2005 Jul 1;106(1):59-66
references.pmid: 15755902
references.citation: Cell Stem Cell. 2009 Jul 2;5(1):54-63
references.pmid: 19570514
references.citation: Exp Cell Res. 2009 Jan 1;315(1):50-66
references.pmid: 18992240
references.citation: Stem Cells. 2010 Mar 31;28(3):585-96
references.pmid: 19967788
references.citation: Stem Cells. 2009 Mar;27(3):724-32
references.pmid: 19259939
references.citation: PLoS One. 2011;6(6):e20526
references.pmid: 21694780
references.citation: Biomaterials. 2011 Oct;32(29):6929-45
references.pmid: 21762982
references.citation: Stem Cells. 2007 Jul;25(7):1761-8
references.pmid: 17395769
references.citation: Nat Rev Immunol. 2008 Sep;8(9):726-36
references.pmid: 19172693