Human embryonic stem cells have a unique epigenetic signature

  1. Marina Bibikova1,
  2. Eugene Chudin1,
  3. Bonnie Wu1,
  4. Lixin Zhou1,
  5. Eliza Wickham Garcia1,
  6. Ying Liu2,12,
  7. Soojung Shin2,12,
  8. Todd W. Plaia3,
  9. Jonathan M. Auerbach3,
  10. Dan E. Arking4,
  11. Rodolfo Gonzalez5,
  12. Jeremy Crook6,
  13. Bruce Davidson6,
  14. Thomas C. Schulz7,
  15. Allan Robins7,
  16. Aparna Khanna8,
  17. Peter Sartipy9,
  18. Johan Hyllner9,
  19. Padmavathy Vanguri10,
  20. Smita Savant-Bhonsale10,
  21. Alan K. Smith11,
  22. Aravinda Chakravarti4,
  23. Anirban Maitra4,
  24. Mahendra Rao2,12,
  25. David L. Barker1,
  26. Jeanne F. Loring5, and
  27. Jian-Bing Fan1,13
  1. 1Illumina, Inc., San Diego, California 92121, USA;
  2. 2Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA;
  3. 3Stem Cell Center, American Type Culture Collection, Manassas, Virginia 20108, USA;
  4. 4McKusick—Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA;
  5. 5Stem Cell Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA;
  6. 6ES Cell International, The Gemini 117610, Singapore;
  7. 7BresaGen, Inc., Athens, Georgia 30605, USA;
  8. 8Reliance Life Sciences Pvt. Ltd., Mumbai 400 701, India;
  9. 9Cellartis AB, 413 46 Goteborg, Sweden;
  10. 10Theradigm, Inc., Baltimore, Maryland 21227, USA;
  11. 11Cognate Therapeutics, Inc., Baltimore, Maryland 21227, USA

    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.

    Footnotes

    • ↵12 Present address: Invitrogen, Inc., Carlsbad, CA 92008, USA.

    • ↵13 Corresponding author.

      ↵13 E-mail jfan{at}illumina.com; fax (858) 202-4680.

    • Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.5319906. Freely available online through the Genome Research Open Access option.

    • Supplemental material is available online at www.genome.org.

      • Received March 24, 2006.
      • Accepted June 22, 2006.

    • Freely available online through the Genome Research Open Access option.

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    1. Published in Advance August 9, 2006, doi: 10.1101/gr.5319906 Genome Res. 16: 1075-1083 Copyright © 2006, Cold Spring Harbor Laboratory Press

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