In:
Nature Communications, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2018-10-02)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2041-1723
DOI:
10.1038/s41467-018-06398-5
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2018
ZDB Id:
2553671-0
