title: Stability of genomic imprinting in human induced pluripotent stem cells.
abstract: BACKGROUND
  hiPSCs are generated through epigenetic reprogramming of somatic tissue. Genomic imprinting is an epigenetic phenomenon through which monoallelic gene expression is regulated in a parent-of-origin-specific manner. Reprogramming relies on the successful erasure of marks of differentiation while maintaining those required for genomic imprinting. Loss of imprinting (LOI), which occurs in many types of malignant tumors, would hinder the clinical application of hiPSCs.
  
  
  RESULTS
  We examined the imprinting status, expression levels and DNA methylation status of eight imprinted genes in five independently generated hiPSCs. We found a low frequency of LOI in some lines. Where LOI was identified in an early passage cell line, we found that this was maintained through subsequent passages of the cells. Just as normal imprints are maintained in long-term culture, this work suggests that abnormal imprints are also stable in culture.
  
  
  CONCLUSIONS
  Analysis of genomic imprints in hiPSCs is a necessary safety step in regenerative medicine, with relevance both to the differentiation potential of these stem cells and also their potential tumorigenic properties.
authors: Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.
authors: Hitoshi
authors: H
authors: Hiura
authors: Masashi
authors: M
authors: Toyoda
authors: Hiroaki
authors: H
authors: Okae
authors: Masahiro
authors: M
authors: Sakurai
authors: Naoko
authors: N
authors: Miyauchi
authors: Akiko
authors: A
authors: Sato
authors: Nobutaka
authors: N
authors: Kiyokawa
authors: Hajime
authors: H
authors: Okita
authors: Yoshitaka
authors: Y
authors: Miyagawa
authors: Hidenori
authors: H
authors: Akutsu
authors: Koichiro
authors: K
authors: Nishino
authors: Akihiro
authors: A
authors: Umezawa
authors: Takahiro
authors: T
authors: Arima
mesh_terms: D019175:DNA Methylation; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D042822:Genomic Instability; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019656:Loss of Heterozygosity
chemical_list: D056572:Histone Deacetylase Inhibitors
references: Cell Stem Cell. 2009 Jul 2;5(1):111-23
references: 19570518
references: Science. 2005 Mar 25;307(5717):1976-8
references: 15731405
references: Trends Genet. 2005 Aug;21(8):457-65
references: 15990197
references: Cancer Sci. 2006 Nov;97(11):1147-54
references: 16965397
references: Endocrinology. 2009 Sep;150(9):4003-11
references: 19574400
references: Nat Rev Genet. 2008 Feb;9(2):129-40
references: 18197165
references: Curr Opin Genet Dev. 2010 Apr;20(2):164-70
references: 20153958
references: Proc Natl Acad Sci U S A. 2008 May 13;105(19):7004-9
references: 18458333
references: Cell. 2007 Nov 30;131(5):861-72
references: 18035408
references: Mol Pathol. 1998 Aug;51(4):185-90
references: 9893743
references: Nat Genet. 2012 Mar 04;44(4):398-405, S1-2
references: 22387999
references: Genome Res. 2008 Aug;18(8):1270-81
references: 18480470
references: Annu Rev Genet. 1986;20:231-51
references: 2880556
references: Genome Res. 2000 Nov;10(11):1711-8
references: 11076856
references: Cell Stem Cell. 2009 Apr 3;4(4):289-300
references: 19341619
references: Curr Top Microbiol Immunol. 2000;249:87-99
references: 10802940
references: Nature. 1993 Apr 22;362(6422):749-51
references: 8097018
references: Nat Genet. 1999 Feb;21(2):163-7
references: 9988266
references: Nature. 2010 May 13;465(7295):175-81
references: 20418860
references: Cancer Res. 1999 Nov 1;59(21):5449-51
references: 10554015
references: Science. 1998 Nov 6;282(5391):1145-7
references: 9804556
references: Growth Horm IGF Res. 2007 Apr;17(2):130-6
references: 17306581
references: Adv Cancer Res. 2008;100:133-58
references: 18620095
references: Mol Carcinog. 2001 May;31(1):1-9
references: 11398192
references: Nat Rev Genet. 2009 Dec;10(12):878-83
references: 19859062
references: Curr Opin Cell Biol. 2007 Jun;19(3):281-9
references: 17467259
references: Int J Cancer. 2005 Jul 10;115(5):690-700
references: 15751035
references: PLoS Genet. 2011 May;7(5):e1002085
references: 21637780
references: Trends Genet. 2008 Jun;24(6):306-16
references: 18471925
references: Exp Cell Res. 2009 Oct 1;315(16):2727-40
references: 19559696
references: Genes Cells. 2001 Mar;6(3):237-47
references: 11260267
references: Nat Genet. 2009 Dec;41(12):1350-3
references: 19881528
references: Nucleic Acids Res. 2010 Aug;38(15):4929-45
references: 20385583
references: Hum Mol Genet. 2007 Nov 1;16(21):2542-51
references: 17636251
references: Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R243-51
references: 17911167
references: Cancer Res. 1999 Apr 1;59(7 Suppl):1743s-1746s
references: 10197590
references: J Hum Genet. 2000;45(2):96-7
references: 10721672
references: Cell Stem Cell. 2008 Sep 11;3(3):340-5
references: 18786420
references: Nat Genet. 2004 Dec;36(12):1291-5
references: 15516931
references: Stem Cells. 2009 Nov;27(11):2686-90
references: 19711451
references: Genes Cells. 2009 Dec;14(12):1395-404
references: 19912344
references: Hum Mol Genet. 1999 Jul;8(7):1209-17
references: 10369866
references: Cell. 1998 May 1;93(3):309-12
references: 9590162
references: Nat Genet. 2004 Dec;36(12):1296-300
references: 15516932
references: Hum Mol Genet. 1997 Oct;6(11):1873-8
references: 9302265
references: Nature. 2008 Jul 3;454(7200):49-55
references: 18509334
references: Mol Biol Cell. 2007 May;18(5):1586-94
references: 17314403
references: Nat Biotechnol. 2010 Aug;28(8):848-55
references: 20644536
references: Stem Cells Dev. 2011 Mar;20(3):451-63
references: 20923371
references: Crit Rev Oncol Hematol. 2009 Jan;69(1):28-44
references: 18656380
references: PLoS One. 2009 Sep 18;4(9):e7076
references: 19763270