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The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences

Author

Listed:
  • N. Ari Wijetunga

    (Albert Einstein College of Medicine)

  • Fabien Delahaye

    (Albert Einstein College of Medicine)

  • Yong M. Zhao

    (Albert Einstein College of Medicine)

  • Aaron Golden

    (Albert Einstein College of Medicine)

  • Jessica C. Mar

    (Albert Einstein College of Medicine)

  • Francine H. Einstein

    (Albert Einstein College of Medicine)

  • John M. Greally

    (Albert Einstein College of Medicine)

Abstract

The mechanism and significance of epigenetic variability in the same cell type between healthy individuals are not clear. Here we purify human CD34+ haematopoietic stem and progenitor cells (HSPCs) from different individuals and find that there is increased variability of DNA methylation at loci with properties of promoters and enhancers. The variability is especially enriched at candidate enhancers near genes transitioning between silent and expressed states, and encoding proteins with leukocyte differentiation properties. Our findings of increased variability at loci with intermediate DNA methylation values, at candidate ‘poised’ enhancers and at genes involved in HSPC lineage commitment suggest that CD34+ cell subtype heterogeneity between individuals is a major mechanism for the variability observed. Epigenomic studies performed on cell populations, even when purified, are testing collections of epigenomes, or meta-epigenomes. Our findings show that meta-epigenomic approaches to data analysis can provide insights into cell subpopulation structure.

Suggested Citation

  • N. Ari Wijetunga & Fabien Delahaye & Yong M. Zhao & Aaron Golden & Jessica C. Mar & Francine H. Einstein & John M. Greally, 2014. "The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6195
    DOI: 10.1038/ncomms6195
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