SENS PubMed Publication Search
A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation.
Nat Commun. 2018 Oct 2;9(1):4047. doi: 10.1038/s41467-018-06398-5
Sheng C, Jungverdorben J, Wiethoff H, Lin Q, Flitsch LJ, Eckert D, Hebisch M, Fischer J, Kesavan J, Weykopf B, Schneider L, Holtkamp D, Beck H, Till A, Wüllner U, Ziller MJ, Wagner W, Peitz M, Brüstle O
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.
PMID: 30279449
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168501/