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@ARTICLE{Sheng:140242,
      author       = {Sheng, Chao and Jungverdorben, Johannes and Wiethoff,
                      Hendrik and Lin, Qiong and Flitsch, Lea J and Eckert,
                      Daniela and Hebisch, Matthias and Fischer, Julia and
                      Kesavan, Jaideep and Weykopf, Beatrice and Schneider, Linda
                      and Holtkamp, Dominik and Beck, Heinz and Till, Andreas and
                      Wüllner, Ullrich and Ziller, Michael J and Wagner, Wolfgang
                      and Peitz, Michael and Brüstle, Oliver},
      title        = {{A} stably self-renewing adult blood-derived induced neural
                      stem cell exhibiting patternability and epigenetic
                      rejuvenation.},
      journal      = {Nature Communications},
      volume       = {9},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DZNE-2020-06564},
      pages        = {4047},
      year         = {2018},
      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.},
      keywords     = {Aging: genetics / Aging: metabolism / DNA Methylation /
                      Epigenesis, Genetic / Humans / Induced Pluripotent Stem
                      Cells / Machado-Joseph Disease: blood / Neural Stem Cells /
                      Peripheral Blood Stem Cells},
      cin          = {Cell Programming Unit / AG Wüllner},
      ddc          = {500},
      cid          = {I:(DE-2719)1013013 / I:(DE-2719)1011302},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30279449},
      pmc          = {pmc:PMC6168501},
      doi          = {10.1038/s41467-018-06398-5},
      url          = {https://pub.dzne.de/record/140242},
}