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

• DOI: 10.1038/s41467-018-06398-5
• Publication Date: 2018-09-26T15:58:38Z
• Authors: Chao Sheng; Johannes Jungverd...; Hendrik Wiethoff; Qiong Lin; Lea J. Flitsch; Daniela Eckert; Matthias Hebisch; Julia Fischer; Jaideep Kesavan; Beatrice Weykopf; Linda Schneider; Dominik Holtkamp; Heinz Beck; Andreas Till; Ullrich Wüllner; Michael J. Ziller; Wolfgang Wagner; Michael Peitz; Oliver Brüstle
• Keywords: Aging; Science; Q; Induced Pluripotent Stem Cells; Machado-Joseph Disease; DNA Methylation; Article; Epigenesis, Genetic; blood [Machado-Joseph Disease]; Neural Stem Cells; 13. Climate action; genetics [Aging]; Peripheral Blood Stem Cells; Humans; ddc:500; metabolism [Aging]

Recent reports suggest that induced neurons (iNs), but not 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 neural cells (iNSCs). Employing restricted integration-free expression SOX2 c-MYC, generated a fully functional, bona fide NSC population from adult blood remains highly responsive to regional patterning cues. Upon conversion, low passage iNSCs display profound loss age-related DNA methylation signatures, which further erode across extended passaging, thereby approximating age isogenic iPSC-derived precursors. This rejuvenation is accompanied by lack absence cellular hallmarks. We find be competent for modeling pathological protein aggregation neurotransplantation, depicting blood-to-NSC conversion as rapid alternative route both disease neuroregeneration.