English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
Add to Basket
  Local TagsRelease HistoryDetailsSummary

Released
Journal Article

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

MPS-Authors
/persons/resource/persons203557

Ziller,  Michael J.
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

41467_2018_Article_6398.pdf
(Publisher version), 6MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Sheng, C., Jungverdorben, J., Wiethoff, H., Lin, Q., Flitsch, L. J., Eckert, D., et al. (2018). A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation. NATURE COMMUNICATIONS, 9(1): 4047. doi:10.1038/s41467-018-06398-5.


Cite as: https://hdl.handle.net/21.11116/0000-0003-6FB0-A
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 ageassociated 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.