%0 Journal Article
%A Sheng, Chao
%A Jungverdorben, Johannes
%A Wiethoff, Hendrik
%A Lin, Qiong
%A Flitsch, Lea J
%A Eckert, Daniela
%A Hebisch, Matthias
%A Fischer, Julia
%A Kesavan, Jaideep
%A Weykopf, Beatrice
%A Schneider, Linda
%A Holtkamp, Dominik
%A Beck, Heinz
%A Till, Andreas
%A Wüllner, Ullrich
%A Ziller, Michael J
%A Wagner, Wolfgang
%A Peitz, Michael
%A Brüstle, Oliver
%T A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation.
%J Nature Communications
%V 9
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DZNE-2020-06564
%P 4047
%D 2018
%X 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.
%K Aging: genetics
%K Aging: metabolism
%K DNA Methylation
%K Epigenesis, Genetic
%K Humans
%K Induced Pluripotent Stem Cells
%K Machado-Joseph Disease: blood
%K Neural Stem Cells
%K Peripheral Blood Stem Cells
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30279449
%2 pmc:PMC6168501
%R 10.1038/s41467-018-06398-5
%U https://pub.dzne.de/record/140242