TY  - JOUR
AU  - Sheng, Chao
AU  - Jungverdorben, Johannes
AU  - Wiethoff, Hendrik
AU  - Lin, Qiong
AU  - Flitsch, Lea J
AU  - Eckert, Daniela
AU  - Hebisch, Matthias
AU  - Fischer, Julia
AU  - Kesavan, Jaideep
AU  - Weykopf, Beatrice
AU  - Schneider, Linda
AU  - Holtkamp, Dominik
AU  - Beck, Heinz
AU  - Till, Andreas
AU  - Wüllner, Ullrich
AU  - Ziller, Michael J
AU  - Wagner, Wolfgang
AU  - Peitz, Michael
AU  - Brüstle, Oliver
TI  - A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation.
JO  - Nature Communications
VL  - 9
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2020-06564
SP  - 4047
PY  - 2018
AB  - 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.
KW  - Aging: genetics
KW  - Aging: metabolism
KW  - DNA Methylation
KW  - Epigenesis, Genetic
KW  - Humans
KW  - Induced Pluripotent Stem Cells
KW  - Machado-Joseph Disease: blood
KW  - Neural Stem Cells
KW  - Peripheral Blood Stem Cells
LB  - PUB:(DE-HGF)16
C6  - pmid:30279449
C2  - pmc:PMC6168501
DO  - DOI:10.1038/s41467-018-06398-5
UR  - https://pub.dzne.de/record/140242
ER  -