title: Epigenetic marks define the lineage and differentiation potential of two distinct neural crest-derived intermediate odontogenic progenitor populations.
abstract: Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF). ChIP on chip assays revealed substantial H3K27me3-mediated repression of odontoblast lineage genes DSPP and dentin matrix protein 1 (DMP1) in DF cells, but not in DP cells. Mineralization inductive conditions caused steep increases of mineralization and patterning gene expression levels in DP cells when compared to DF cells. In contrast, mineralization induction resulted in a highly dynamic histone modification response in DF cells, while there was only a subdued effect in DP cells. Both DF and DP progenitors featured H3K4me3-active marks on the promoters of early mineralization genes RUNX2, MSX2, and DLX5, while OSX, IBSP, and BGLAP promoters were enriched for H3K9me3 or H3K27me3. Compared to DF cells, DP cells expressed higher levels of three pluripotency-associated genes, OCT4, NANOG, and SOX2. Finally, gene ontology comparison of bivalent marks unique for DP and DF cells highlighted cell-cell attachment genes in DP cells and neurogenesis genes in DF cells. In conclusion, the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression of DSPP and DMP1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages.
authors: UIC Brodie Laboratory for Craniofacial Genetics, UIC College of Dentistry, Chicago, Illinois 60612, USA.
authors: Gokul
authors: G
authors: Gopinathan
authors: Antonia
authors: A
authors: Kolokythas
authors: Xianghong
authors: X
authors: Luan
authors: Thomas G H
authors: TG
authors: Diekwisch
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D002648:Child; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D003795:Dental Sac / Q000166:cytology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D009928:Organ Specificity; D010012:Osteogenesis / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D000099311:Dentin Sialophosphoprotein
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human; C524220:KDM6B protein, human
references: J Bone Miner Res. 2002 Aug;17(8):1441-51
references: 12162498
references: Nature. 2007 May 24;447(7143):425-32
references: 17522676
references: J Dent Res. 2003 Mar;82(3):166-71
references: 12598543
references: J Endod. 2010 May;36(5):781-9
references: 20416419
references: Periodontol 2000. 1997 Feb;13:9-19
references: 9567921
references: Proc Finn Dent Soc. 1992;88 Suppl 1:357-68
references: 1508891
references: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4516-21
references: 11287660
references: Mech Dev. 1997 Oct;67(2):111-23
references: 9392510
references: Mol Cell Biol. 2005 Apr;25(7):2525-38
references: 15767660
references: PLoS Genet. 2011 Apr;7(4):e1001369
references: 21533021
references: Biol Rev Camb Philos Soc. 1990 Aug;65(3):277-373
references: 2205303
references: Nat Rev Genet. 2002 Sep;3(9):662-73
references: 12209141
references: J Comp Neurol. 1985 Jan 22;231(4):500-18
references: 3968252
references: Mol Cell Proteomics. 2012 May;11(5):128-37
references: 22442256
references: Stem Cells Dev. 2006 Aug;15(4):595-608
references: 16978062
references: J Physiol. 1993 May;464:711-23
references: 8229826
references: Ann N Y Acad Sci. 2011 Nov;1237:47-52
references: 22082364
references: Cell. 1992 Jun 12;69(6):915-26
references: 1606615
references: Microsc Res Tech. 2002 Dec 1;59(5):449-59
references: 12430171
references: Nat Protoc. 2012 Sep;7(9):1728-40
references: 22936215
references: Nat Rev Genet. 2004 Jun;5(6):446-55
references: 15153997
references: J Craniofac Genet Dev Biol. 1994 Oct-Dec;14(4):207-16
references: 7883867
references: Genome Biol. 2009;10(10):R109
references: 19814794
references: Nat Rev Cancer. 2004 Feb;4(2):143-53
references: 14732866
references: Genome Res. 2012 Jun;22(6):1128-38
references: 22466170
references: J Musculoskelet Neuronal Interact. 2005 Oct-Dec;5(4):325-7
references: 16340123
references: J Comp Neurol. 2011 Nov 1;519(16):3306-26
references: 21681747
references: Eur J Orthod. 2008 Jun;30(3):299-306
references: 18540017
references: Science. 2007 Apr 27;316(5824):608-11
references: 17463290
references: Eur J Oral Sci. 2008 Aug;116(4):312-8
references: 18705798
references: J Bone Miner Res. 2004 Sep;19(9):1379-94
references: 15312238
references: Minerva Stomatol. 1999 Jul-Aug;48(7-8):325-31
references: 10568109
references: Clin Oral Investig. 2009 Dec;13(4):383-91
references: 19252934
references: Cold Spring Harb Protoc. 2009 Mar;2009(3):pdb.prot5170
references: 20147105
references: Epigenetics. 2010 Aug 16;5(6):476-82
references: 20574163
references: Dev Biol. 2012 Jun 15;366(2):244-54
references: 22542602
references: Acta Odontol Scand. 1980;38(1):41-50
references: 6929638
references: Cell. 2006 Apr 21;125(2):315-26
references: 16630819
references: Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R47-58
references: 15809273
references: Cell. 2007 Nov 30;131(5):834-5
references: 18045526
references: Nat Rev Genet. 2007 Jan;8(1):9-22
references: 17173055
references: J Biol Chem. 2005 Aug 19;280(33):29717-27
references: 15980071
references: Int Endod J. 2008 Nov;41(11):933-8
references: 19133082
references: J Dent Res. 2009 Sep;88(9):781-91
references: 19767574
references: Connect Tissue Res. 1995;32(1-4):1-8
references: 7554904
references: Stem Cells Int. 2011;2011:201371
references: 21772852
references: J Histochem Cytochem. 2007 Feb;55(2):127-40
references: 17015623
references: J Int Acad Periodontol. 2005 Oct;7(4):102-7
references: 16245640
references: Stem Cells Dev. 2012 Jul 20;21(11):1936-47
references: 22107079
references: Hum Mol Genet. 2008 Apr 15;17(R1):R28-36
references: 18632693
references: Nat Cell Biol. 2007 Jan;9(1):2-6
references: 17199124
references: Curr Opin Genet Dev. 2002 Apr;12(2):198-209
references: 11893494
references: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13625-30
references: 11087820
references: Genes Dev. 2009 Nov 1;23(21):2484-9
references: 19884255
references: Microsc Res Tech. 2002 Dec 1;59(5):373-95
references: 12430167
references: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references: 9843981
references: Crit Rev Oral Biol Med. 2004 Jan 1;15(1):13-27
references: 14761897
references: Arch Oral Biol. 2010 Jan;55(1):68-76
references: 19942210
references: Stem Cells Dev. 2009 Jun;18(5):725-36
references: 18771397
references: Adv Dent Res. 2001 Aug;15:8-13
references: 12640731
references: Science. 1996 Aug 2;273(5275):654-7
references: 8662558
references: Nat Protoc. 2006;1(2):729-48
references: 17406303
references: Stem Cells Dev. 2011 Jan;20(1):39-52
references: 20604680
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Mol Biol Cell. 2010 Jun 15;21(12):2066-77
references: 20410135
references: Hum Mol Genet. 2008 Apr 15;17(R1):R23-7
references: 18632692
references: Tissue Eng Part C Methods. 2012 Nov;18(11):821-30
references: 22563788
references: Development. 1999 Jul;126(13):2911-20
references: 10357935
references: Adv Dent Res. 2011 Jul;23(3):270-4
references: 21677077
references: Evol Dev. 2009 May-Jun;11(3):247-59
references: 19469852
references: Am J Pathol. 2002 Jun;160(6):2123-33
references: 12057916
references: Genes Dev. 2011 Apr 1;25(7):742-54
references: 21460038
references: Bone. 2010 Jun;46(6):1639-51
references: 20193787
references: Gene Ther. 2002 Jun;9(12):814-8
references: 12040463
references: Genes Dev. 2002 Jan 1;16(1):6-21
references: 11782440
references: Brief Bioinform. 2013 Mar;14(2):178-92
references: 22517427
references: J Cell Physiol. 2010 Apr;223(1):123-33
references: 20039267