Journal Article

DZNE-2020-06564

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation.

Sheng, C. (First author)DZNE* ; Jungverdorben, J.DZNE* ; Wiethoff, H. ; Lin, Q. ; Flitsch, L. J. ; Eckert, D. ; Hebisch, M.DZNE* ; Fischer, J. ; Kesavan, J. ; Weykopf, B. ; Schneider, L. ; Holtkamp, D. ; Beck, H. ; Till, A. ; Wüllner, U.DZNE* ; Ziller, M. J. ; Wagner, W. ; Peitz, M. (Corresponding author)DZNE* ; Brüstle, O.

2018
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-018-06398-5

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.

Keyword(s): Aging: genetics (MeSH) ; Aging: metabolism (MeSH) ; DNA Methylation (MeSH) ; Epigenesis, Genetic (MeSH) ; Humans (MeSH) ; Induced Pluripotent Stem Cells (MeSH) ; Machado-Joseph Disease: blood (MeSH) ; Neural Stem Cells (MeSH) ; Peripheral Blood Stem Cells (MeSH)

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Contributing Institute(s):

1. Cell Programming Unit (Cell Programming Unit)
2. Biomarker Parkinson's Disease (AG Wüllner)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2018

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