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000140242 1001_ $$0P:(DE-2719)2811310$$aSheng, Chao$$b0$$eFirst author$$udzne
000140242 245__ $$aA stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation.
000140242 260__ $$a[London]$$bNature Publishing Group UK$$c2018
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000140242 520__ $$aRecent 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.
000140242 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000140242 542__ $$2Crossref$$i2018-10-02$$uhttps://creativecommons.org/licenses/by/4.0
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000140242 650_2 $$2MeSH$$aAging: genetics
000140242 650_2 $$2MeSH$$aAging: metabolism
000140242 650_2 $$2MeSH$$aDNA Methylation
000140242 650_2 $$2MeSH$$aEpigenesis, Genetic
000140242 650_2 $$2MeSH$$aHumans
000140242 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells
000140242 650_2 $$2MeSH$$aMachado-Joseph Disease: blood
000140242 650_2 $$2MeSH$$aNeural Stem Cells
000140242 650_2 $$2MeSH$$aPeripheral Blood Stem Cells
000140242 7001_ $$0P:(DE-2719)2811320$$aJungverdorben, Johannes$$b1$$udzne
000140242 7001_ $$aWiethoff, Hendrik$$b2
000140242 7001_ $$aLin, Qiong$$b3
000140242 7001_ $$aFlitsch, Lea J$$b4
000140242 7001_ $$aEckert, Daniela$$b5
000140242 7001_ $$0P:(DE-2719)2811349$$aHebisch, Matthias$$b6$$udzne
000140242 7001_ $$aFischer, Julia$$b7
000140242 7001_ $$aKesavan, Jaideep$$b8
000140242 7001_ $$0P:(DE-HGF)0$$aWeykopf, Beatrice$$b9
000140242 7001_ $$aSchneider, Linda$$b10
000140242 7001_ $$aHoltkamp, Dominik$$b11
000140242 7001_ $$0P:(DE-HGF)0$$aBeck, Heinz$$b12
000140242 7001_ $$aTill, Andreas$$b13
000140242 7001_ $$0P:(DE-2719)2000056$$aWüllner, Ullrich$$b14$$udzne
000140242 7001_ $$aZiller, Michael J$$b15
000140242 7001_ $$aWagner, Wolfgang$$b16
000140242 7001_ $$0P:(DE-2719)9000249$$aPeitz, Michael$$b17$$eCorresponding author$$udzne
000140242 7001_ $$0P:(DE-HGF)0$$aBrüstle, Oliver$$b18
000140242 77318 $$2Crossref$$3journal-article$$a10.1038/s41467-018-06398-5$$b : Springer Science and Business Media LLC, 2018-10-02$$n1$$p4047$$tNature Communications$$v9$$x2041-1723$$y2018
000140242 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-018-06398-5$$gVol. 9, no. 1, p. 4047$$n1$$p4047$$q9:1<4047$$tNature Communications$$v9$$x2041-1723$$y2018
000140242 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168501
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