Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells

被引：28
|
作者：
Butcher, Lee M. [1 ,2 ]
Ito, Mitsuteru [3 ]
Brimpari, Minodora [4 ,5 ]
Morris, Tiffany J. [1 ,6 ]
Soares, Filipa A. C. [4 ,5 ,7 ]
Ahrlund-Richter, Lars [8 ]
Carey, Nessa [9 ]
Vallier, Ludovic [4 ,5 ,7 ]
Ferguson-Smith, Anne C. [3 ]
Beck, Stephan [1 ]
机构：
[1] UCL, UCL Canc Inst, 72 Huntley St, London WC1E 6BT, England
[2] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London W12 0NN, England
[3] Univ Cambridge, Dept Genet, Downing St, Cambridge CB2 3EH, England
[4] Univ Cambridge, Anne McLaren Lab, Dept Surg, Wellcome Trust, Cambridge CB2 0SZ, England
[5] Univ Cambridge, Med Res Council, Stem Cell Inst, Cambridge CB2 0SZ, England
[6] Cambridge Epigenetix, Jonas Webb Bldg,Babraham Campus, Cambridge CB22 3AT, England
[7] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England
[8] Karolinska Inst, Div Paediat Oncol, Dept Womens & Childrens Hlth, S-17176 Stockholm, Sweden
[9] PraxisUnico, Jeffreys Bldg,St Johns Innovat Pk, Cambridge CB4 0DE, England
来源：
NATURE COMMUNICATIONS | 2016年 / 7卷
基金：
英国工程与自然科学研究理事会; 英国医学研究理事会; 英国惠康基金;
关键词：
SP1; BINDING; CPG ISLAND; METHYLOME; EPIGENOME; GALAXY; MAPS;
D O I：
10.1038/ncomms10458
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Delta beta = 13%, P<7.4 x 10(-4)) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Delta beta = 23%, P<9.1 x 10(-6)) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout.
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页数：8
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