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Sheng, Chao; Jungverdorben, Johannes; Wiethoff, Hendrik; Lin, Qiong; Flitsch, Lea J.; Eckert, Daniela; Hebisch, Matthias; Fischer, Julia; Kesavan, Jaideep; Weykopf, Beatrice; Schneider, Linda; Holtkamp, Dominik; Beck, Heinz; Till, Andreas; Wüllner, Ullrich; Ziller, Michael J.; Wagner, Wolfgang; Peitz, Michael; Brüstle, Oliver

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

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  • Media type: E-Article
  • Title: A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation
  • Contributor: Sheng, Chao; Jungverdorben, Johannes; Wiethoff, Hendrik; Lin, Qiong; Flitsch, Lea J.; Eckert, Daniela; Hebisch, Matthias; Fischer, Julia; Kesavan, Jaideep; Weykopf, Beatrice; Schneider, Linda; Holtkamp, Dominik; Beck, Heinz; Till, Andreas; Wüllner, Ullrich; Ziller, Michael J.; Wagner, Wolfgang; Peitz, Michael; Brüstle, Oliver
  • imprint: Springer Science and Business Media LLC, 2018
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-018-06398-5
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
  • Access State: Open Access