Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts

  1. Christine J Huh
  2. Bo Zhang
  3. Matheus Victor
  4. Sonika Dahiya
  5. Luis FZ Batista
  6. Steve Horvath
  7. Andrew S Yoo  Is a corresponding author
  1. Washington University School of Medicine, United States
  2. University of California Los Angeles, United States

Abstract

Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a recently demonstrated microRNA-based cellular reprogramming approach, human fibroblasts from postnatal to near centenarian donors can be efficiently converted into neurons that maintain multiple age-associated signatures. Application of an epigenetic biomarker of aging (referred to as epigenetic clock) to DNA methylation data revealed that the epigenetic ages of fibroblasts were highly correlated with corresponding age estimates of reprogrammed neurons. Transcriptome and microRNA profiles reveal genes differentially expressed between young and old neurons. Further analyses of oxidative stress, DNA damage and telomere length exhibit the retention of age-associated cellular properties in converted neurons from corresponding fibroblasts. Our results collectively demonstrate the maintenance of age after neuronal conversion.

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Article and author information

Author details

  1. Christine J Huh

    Program in Molecular and Cellular Biology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Bo Zhang

    Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Matheus Victor

    Program in Neuroscience, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sonika Dahiya

    Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Luis FZ Batista

    Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Steve Horvath

    Department of Human Genetics, University of California Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Andrew S Yoo

    Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States
    For correspondence
    yooa@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0304-3247

Funding

National Institutes of Health (DP2NS083372-01)

  • Andrew S Yoo

Ellison Medical Foundation (AG-NS-0878-12)

  • Andrew S Yoo

National Institutes of Health (K99/R00, 4R00HL114732-03)

  • Luis FZ Batista

Washington University in St. Louis (DDRCC, NIDDK P30 DK052574)

  • Luis FZ Batista

National Institutes of Health (1U34AG051425-01)

  • Steve Horvath

National Institutes of Health (5R01, AG042511-02)

  • Steve Horvath

National Institute on Drug Abuse (R25 DA027995)

  • Bo Zhang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: June 9, 2016
  2. Accepted: September 15, 2016
  3. Accepted Manuscript published: September 20, 2016 (version 1)
  4. Version of Record published: October 17, 2016 (version 2)

Copyright

© 2016, Huh et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Christine J Huh
  2. Bo Zhang
  3. Matheus Victor
  4. Sonika Dahiya
  5. Luis FZ Batista
  6. Steve Horvath
  7. Andrew S Yoo
(2016)
Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts
eLife 5:e18648.
https://doi.org/10.7554/eLife.18648
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