Home LiteratureArticle Details
PMID: 16899657 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Human embryonic stem cells have a unique epigenetic signature.

Genome research ·Vol. 16 ·No. 9 ·2006-09-00 ·Pages 1075-83

Bibikova M, Chudin E, Wu B, Zhou L, Garcia EW, Liu Y, Shin S, Plaia TW, Auerbach JM, Arking DE, Gonzalez R, Crook J, Davidson B, Schulz TC, Robins A, Khanna A, Sartipy P, Hyllner J, Vanguri P, Savant-Bhonsale S, Smith AK, Chakravarti A, Maitra A, Rao M, Barker DL, Loring JF, Fan JB

Abstract

Human embryonic stem (hES) cells originate during an embryonic period of active epigenetic remodeling. DNA methylation patterns are likely to be critical for their self-renewal and pluripotence. We compared the DNA methylation status of 1536 CpG sites (from 371 genes) in 14 independently isolated hES cell lines with five other cell types: 24 cancer cell lines, four adult stem cell populations, four lymphoblastoid cell lines, five normal human tissues, and an embryonal carcinoma cell line. We found that the DNA methylation profile clearly distinguished the hES cells from all of the other cell types. A subset of 49 CpG sites from 40 genes contributed most to the differences among cell types. Another set of 25 sites from 23 genes distinguished hES cells from normal differentiated cells and can be used as biomarkers to monitor differentiation. Our results indicate that hES cells have a unique epigenetic signature that may contribute to their developmental potential.

MeSH Terms
Cell Differentiation Cell Line Cell Line, Tumor Cell Lineage Cluster Analysis DNA Methylation Embryo, Mammalian/cytology Epigenesis, Genetic Female Humans Male Pluripotent Stem Cells/cytology,metabolism Stem Cells/cytology,metabolism
Authors & Affiliations
27 authors, click to expand affiliations / ORCID
Bibikova Marina
Illumina, Inc., San Diego, California 92121, USA.
Chudin Eugene
Wu Bonnie
Zhou Lixin
Garcia Eliza Wickham
Liu Ying
Shin Soojung
Plaia Todd W
Auerbach Jonathan M
Arking Dan E
Gonzalez Rodolfo
Crook Jeremy
Davidson Bruce
Schulz Thomas C
Robins Allan
Khanna Aparna
Sartipy Peter
Hyllner Johan
Vanguri Padmavathy
Savant-Bhonsale Smita
Smith Alan K
Chakravarti Aravinda
Maitra Anirban
Rao Mahendra
Barker David L
Loring Jeanne F
Fan Jian-Bing
References (40)
40 references, click to expand
  1. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro.
    Nat Biotechnol. 2000 Apr;18(4):399-404 PMID: 10748519
  2. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells.
    Science. 2005 Aug 26;309(5739):1369-73 PMID: 16123299
  3. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future.
    Oncogene. 2002 Aug 12;21(35):5427-40 PMID: 12154405
  4. Between-group analysis of microarray data.
    Bioinformatics. 2002 Dec;18(12):1600-8 PMID: 12490444
  5. Genome-wide analysis of epigenetics in cancer.
    Ann N Y Acad Sci. 2003 Mar;983:101-9 PMID: 12724215
  6. Automatic registration of microarray images. II. Hexagonal grid.
    Bioinformatics. 2003 Sep 22;19(14):1832-6 PMID: 14512355
  7. Gene silencing in cancer in association with promoter hypermethylation.
    N Engl J Med. 2003 Nov 20;349(21):2042-54 PMID: 14627790
  8. Gametes and embryo epigenetic reprogramming affect developmental outcome: implication for assisted reproductive technologies.
    Pediatr Res. 2005 Sep;58(3):437-46 PMID: 16148054
  9. Genomic alterations in cultured human embryonic stem cells.
    Nat Genet. 2005 Oct;37(10):1099-103 PMID: 16142235
  10. Global loss of imprinting leads to widespread tumorigenesis in adult mice.
    Cancer Cell. 2005 Oct;8(4):275-85 PMID: 16226703
  11. Global hypomethylation of the genome in XX embryonic stem cells.
    Nat Genet. 2005 Nov;37(11):1274-9 PMID: 16244654
  12. X-inactivation status varies in human embryonic stem cell lines.
    Stem Cells. 2005 Nov-Dec;23(10):1468-78 PMID: 16123389
  13. Establishing standards for the characterization of human embryonic stem cell lines.
    Stem Cells. 2006 Jan;24(1):145-50 PMID: 16253979
  14. Derivation of human embryonic stem cells in defined conditions.
    Nat Biotechnol. 2006 Feb;24(2):185-7 PMID: 16388305
  15. High-throughput DNA methylation profiling using universal bead arrays.
    Genome Res. 2006 Mar;16(3):383-93 PMID: 16449502
  16. Characterization and in vitro differentiation potential of a new human embryonic stem cell line, ReliCellhES1.
    Differentiation. 2006 Mar;74(2-3):81-90 PMID: 16533307
  17. Clonal derivation and characterization of human embryonic stem cell lines.
    J Biotechnol. 2006 Apr 20;122(4):511-20 PMID: 16324761
  18. Spontaneous differentiation of germ cells from human embryonic stem cells in vitro.
    Hum Mol Genet. 2004 Apr 1;13(7):727-39 PMID: 14962983
  19. Derivation of embryonic stem-cell lines from human blastocysts.
    N Engl J Med. 2004 Mar 25;350(13):1353-6 PMID: 14999088
  20. Derivation, characterization, and differentiation of human embryonic stem cells.
    Stem Cells. 2004;22(3):367-76 PMID: 15153613
  21. Propagation and maintenance of undifferentiated human embryonic stem cells.
    Stem Cells Dev. 2004 Jun;13(3):243-53 PMID: 15186720
  22. Stem-cell consequences of embryo epigenetic defects.
    Lancet. 2004 Jul 10-16;364(9429):206-8 PMID: 15246736
  23. Highly parallel SNP genotyping.
    Cold Spring Harb Symp Quant Biol. 2003;68:69-78 PMID: 15338605
  24. Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro.
    Lab Invest. 1984 Feb;50(2):147-62 PMID: 6694356
  25. Embryonic stem cell lines derived from human blastocysts.
    Science. 1998 Nov 6;282(5391):1145-7 PMID: 9804556
  26. Establishing the epigenetic status of the Prader-Willi/Angelman imprinting center in the gametes and embryo.
    Hum Mol Genet. 2004 Nov 15;13(22):2767-79 PMID: 15367489
  27. DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project.
    PLoS Biol. 2004 Dec;2(12):e405 PMID: 15550986
  28. Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001.
    Stem Cells Dev. 2004 Dec;13(6):585-97 PMID: 15684826
  29. Epigenetics and the germline.
    Reproduction. 2005 Feb;129(2):137-49 PMID: 15695608
  30. TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells.
    Development. 2005 Mar;132(6):1273-82 PMID: 15703277
  31. BG01V: a variant human embryonic stem cell line which exhibits rapid growth after passaging and reliable dopaminergic differentiation.
    Restor Neurol Neurosci. 2004;22(6):421-8 PMID: 15798361
  32. From genome to epigenome.
    Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R3-R10 PMID: 15809270
  33. Epigenetic reprogramming in mammals.
    Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R47-58 PMID: 15809273
  34. Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells.
    Nat Methods. 2005 Mar;2(3):185-90 PMID: 15782187
  35. Embryonic stem cell differentiation: emergence of a new era in biology and medicine.
    Genes Dev. 2005 May 15;19(10):1129-55 PMID: 15905405
  36. CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome.
    Nucleic Acids Res. 2005;33(9):2952-61 PMID: 15911630
  37. MADE4: an R package for multivariate analysis of gene expression data.
    Bioinformatics. 2005 Jun 1;21(11):2789-90 PMID: 15797915
  38. The International Stem Cell Initiative: toward benchmarks for human embryonic stem cell research.
    Nat Biotechnol. 2005 Jul;23(7):795-7 PMID: 16003358
  39. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells.
    Nat Genet. 2005 Aug;37(8):853-62 PMID: 16007088
  40. Derivation and spontaneous differentiation of human embryonic stem cells.
    J Anat. 2002 Mar;200(Pt 3):225-32 PMID: 12033726
Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
Published
2006-09-00
Epub
2006-00-09
Pages
1075-83
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC1557765
Subset
IM
Grants
NCI NIH HHS · R44 CA097851 · United States
NCI NIH HHS · R44-CA097851 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com