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A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation

Author

Listed:
  • Chao Sheng

    (University of Bonn Medical Center
    German Center for Neurodegenerative Diseases (DZNE))

  • Johannes Jungverdorben

    (University of Bonn Medical Center
    German Center for Neurodegenerative Diseases (DZNE))

  • Hendrik Wiethoff

    (University of Bonn Medical Center)

  • Qiong Lin

    (RWTH Aachen University Medical School)

  • Lea J. Flitsch

    (University of Bonn Medical Center)

  • Daniela Eckert

    (University of Bonn Medical Center)

  • Matthias Hebisch

    (University of Bonn Medical Center
    German Center for Neurodegenerative Diseases (DZNE))

  • Julia Fischer

    (University of Bonn Medical Center)

  • Jaideep Kesavan

    (University of Bonn Medical Center)

  • Beatrice Weykopf

    (University of Bonn Medical Center)

  • Linda Schneider

    (University of Bonn Medical Center)

  • Dominik Holtkamp

    (University of Bonn Medical Center)

  • Heinz Beck

    (University of Bonn Medical Center)

  • Andreas Till

    (University of Bonn Medical Center)

  • Ullrich Wüllner

    (German Center for Neurodegenerative Diseases (DZNE)
    University of Bonn Medical Center)

  • Michael J. Ziller

    (Max Planck Institute of Psychiatry)

  • Wolfgang Wagner

    (RWTH Aachen University Medical School)

  • Michael Peitz

    (University of Bonn Medical Center
    German Center for Neurodegenerative Diseases (DZNE))

  • Oliver Brüstle

    (University of Bonn Medical Center)

Abstract

Recent reports suggest that induced neurons (iNs), but not induced pluripotent stem cell (iPSC)-derived neurons, largely preserve age-associated traits. Here, we report on the extent of preserved epigenetic and transcriptional aging signatures in directly converted induced neural stem cells (iNSCs). Employing restricted and integration-free expression of SOX2 and c-MYC, we generated a fully functional, bona fide NSC population from adult blood cells that remains highly responsive to regional patterning cues. Upon conversion, low passage iNSCs display a profound loss of age-related DNA methylation signatures, which further erode across extended passaging, thereby approximating the DNA methylation age of isogenic iPSC-derived neural precursors. This epigenetic rejuvenation is accompanied by a lack of age-associated transcriptional signatures and absence of cellular aging hallmarks. We find iNSCs to be competent for modeling pathological protein aggregation and for neurotransplantation, depicting blood-to-NSC conversion as a rapid alternative route for both disease modeling and neuroregeneration.

Suggested Citation

  • Chao Sheng & Johannes Jungverdorben & Hendrik Wiethoff & Qiong Lin & Lea J. Flitsch & Daniela Eckert & Matthias Hebisch & Julia Fischer & Jaideep Kesavan & Beatrice Weykopf & Linda Schneider & Dominik, 2018. "A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06398-5
    DOI: 10.1038/s41467-018-06398-5
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    Cited by:

    1. Ali Doğa Yücel & Vadim N. Gladyshev, 2024. "The long and winding road of reprogramming-induced rejuvenation," Nature Communications, Nature, vol. 15(1), pages 1-9, December.

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