A Panel of CpG Methylation Sites Distinguishes Human Embryonic Stem Cells and Induced Pluripotent Stem Cells

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2014 Feb 11

PMID 24511466

Citations 29

Authors

Kevin Huang

Yin Shen

Zhigang Xue

Marina Bibikova

Craig April

Zhenshan Liu

Linzhao Cheng

Andras Nagy

Matteo Pellegrini

Jian-Bing Fan

Guoping Fan

Affiliations

Soon will be listed here.

Abstract

Whether human induced pluripotent stem cells (hiPSCs) are epigenetically identical to human embryonic stem cells (hESCs) has been debated in the stem cell field. In this study, we analyzed DNA methylation patterns in a large number of hiPSCs (n = 114) and hESCs (n = 155), and identified a panel of 82 CpG methylation sites that can distinguish hiPSCs from hESCs with high accuracy. We show that 12 out of the 82 CpG sites were subject to hypermethylation in part by DNMT3B. Notably, DNMT3B contributes directly to aberrant hypermethylation and silencing of the signature gene, TCERG1L. Overall, we conclude that DNMT3B is involved in a wave of de novo methylation during reprogramming, a portion of which contributes to the unique hiPSC methylation signature. These 82 CpG methylation sites may be useful as biomarkers to distinguish between hiPSCs and hESCs.

Citing Articles

Efficient Generation of Pancreatic Progenitor Cells from Induced Pluripotent Stem Cells Derived from a Non-Invasive and Accessible Tissue Source-The Plucked Hair Follicle.

Fatehi A, Sadat M, Fayyad M, Tang J, Han D, Rogers I Cells. 2024; 13(12.

PMID: 38920642 PMC: 11202038. DOI: 10.3390/cells13121010.

TERT Promoter Methylation Is Oxygen-Sensitive and Regulates Telomerase Activity.

Dogan F, Forsyth N Biomolecules. 2024; 14(1).

PMID: 38275760 PMC: 10813121. DOI: 10.3390/biom14010131.

Mitochondria in Mesenchymal Stem Cells: Key to Fate Determination and Therapeutic Potential.

Liu Y, Wang L, Ai J, Li K Stem Cell Rev Rep. 2024; 20(3):617-636.

PMID: 38265576 DOI: 10.1007/s12015-024-10681-y.

Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation.

Arez M, Eckersley-Maslin M, Klobucar T, von Gilsa Lopes J, Krueger F, Mupo A Nat Commun. 2022; 13(1):5432.

PMID: 36114205 PMC: 9481624. DOI: 10.1038/s41467-022-33013-5.

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

Meijer A, Diepstraten F, Langer T, Broer L, Domingo I, Clemens E NPJ Precis Oncol. 2021; 5(1):64.

PMID: 34262104 PMC: 8280110. DOI: 10.1038/s41698-021-00178-z.

References

Chou B, Mali P, Huang X, Ye Z, Dowey S, Resar L . Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res. 2011; 21(3):518-29. PMC: 3193421. DOI: 10.1038/cr.2011.12. View

Laurent L, Wong E, Li G, Huynh T, Tsirigos A, Ong C . Dynamic changes in the human methylome during differentiation. Genome Res. 2010; 20(3):320-31. PMC: 2840979. DOI: 10.1101/gr.101907.109. View

Nishino K, Toyoda M, Yamazaki-Inoue M, Fukawatase Y, Chikazawa E, Sakaguchi H . DNA methylation dynamics in human induced pluripotent stem cells over time. PLoS Genet. 2011; 7(5):e1002085. PMC: 3102737. DOI: 10.1371/journal.pgen.1002085. View

Doi A, Park I, Wen B, Murakami P, Aryee M, Irizarry R . Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet. 2009; 41(12):1350-3. PMC: 2958040. DOI: 10.1038/ng.471. View

Lister R, Pelizzola M, Dowen R, Hawkins R, Hon G, Tonti-Filippini J . Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009; 462(7271):315-22. PMC: 2857523. DOI: 10.1038/nature08514. View

Ziller M, Muller F, Liao J, Zhang Y, Gu H, Bock C . Genomic distribution and inter-sample variation of non-CpG methylation across human cell types. PLoS Genet. 2011; 7(12):e1002389. PMC: 3234221. DOI: 10.1371/journal.pgen.1002389. View

Chodavarapu R, Feng S, Bernatavichute Y, Chen P, Stroud H, Yu Y . Relationship between nucleosome positioning and DNA methylation. Nature. 2010; 466(7304):388-92. PMC: 2964354. DOI: 10.1038/nature09147. View

Stadler M, Murr R, Burger L, Ivanek R, Lienert F, Scholer A . DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature. 2011; 480(7378):490-5. DOI: 10.1038/nature10716. View

Mikkelsen T, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P . Dissecting direct reprogramming through integrative genomic analysis. Nature. 2008; 454(7200):49-55. PMC: 2754827. DOI: 10.1038/nature07056. View

10.

Hawkins R, Hon G, Lee L, Ngo Q, Lister R, Pelizzola M . Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell. 2010; 6(5):479-91. PMC: 2867844. DOI: 10.1016/j.stem.2010.03.018. View

11.

Chin M, Mason M, Xie W, Volinia S, Singer M, Peterson C . Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell. 2009; 5(1):111-23. PMC: 3448781. DOI: 10.1016/j.stem.2009.06.008. View

12.

Newman A, Cooper J . Lab-specific gene expression signatures in pluripotent stem cells. Cell Stem Cell. 2010; 7(2):258-62. DOI: 10.1016/j.stem.2010.06.016. View

13.

Ruiz S, Diep D, Gore A, Panopoulos A, Montserrat N, Plongthongkum N . Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2012; 109(40):16196-201. PMC: 3479609. DOI: 10.1073/pnas.1202352109. View

14.

Nazor K, Altun G, Lynch C, Tran H, Harness J, Slavin I . Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives. Cell Stem Cell. 2012; 10(5):620-34. PMC: 3348513. DOI: 10.1016/j.stem.2012.02.013. View

15.

Ohi Y, Qin H, Hong C, Blouin L, Polo J, Guo T . Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol. 2011; 13(5):541-9. PMC: 3987913. DOI: 10.1038/ncb2239. View

16.

Stadtfeld M, Maherali N, Breault D, Hochedlinger K . Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell. 2008; 2(3):230-40. PMC: 3538379. DOI: 10.1016/j.stem.2008.02.001. View

17.

Guenther M, Frampton G, Soldner F, Hockemeyer D, Mitalipova M, Jaenisch R . Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell. 2010; 7(2):249-57. PMC: 3010384. DOI: 10.1016/j.stem.2010.06.015. View

18.

Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith Z . Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell. 2011; 144(3):439-52. PMC: 3063454. DOI: 10.1016/j.cell.2010.12.032. View

19.

Lister R, Pelizzola M, Kida Y, Hawkins R, Nery J, Hon G . Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature. 2011; 471(7336):68-73. PMC: 3100360. DOI: 10.1038/nature09798. View

20.

Feng J, Fan G . The role of DNA methylation in the central nervous system and neuropsychiatric disorders. Int Rev Neurobiol. 2009; 89:67-84. DOI: 10.1016/S0074-7742(09)89004-1. View