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@ARTICLE{Reinhardt:136849,
      author       = {Reinhardt, Peter and Glatza, Michael and Hemmer, Kathrin
                      and Tsytsyura, Yaroslav and Thiel, Cora S and Höing,
                      Susanne and Moritz, Sören and Parga, Juan A and Wagner,
                      Lydia and Bruder, Jan M and Wu, Guangming and Schmid,
                      Benjamin and Röpke, Albrecht and Klingauf, Jürgen and
                      Schwamborn, Jens C and Gasser, Thomas and Schöler, Hans R
                      and Sterneckert, Jared},
      title        = {{D}erivation and expansion using only small molecules of
                      human neural progenitors for neurodegenerative disease
                      modeling.},
      journal      = {PLOS ONE},
      volume       = {8},
      number       = {3},
      issn         = {1932-6203},
      address      = {San Francisco, California, US},
      publisher    = {PLOS},
      reportid     = {DZNE-2020-03171},
      pages        = {e59252},
      year         = {2013},
      abstract     = {Phenotypic drug discovery requires billions of cells for
                      high-throughput screening (HTS) campaigns. Because up to
                      several million different small molecules will be tested in
                      a single HTS campaign, even small variability within the
                      cell populations for screening could easily invalidate an
                      entire campaign. Neurodegenerative assays are particularly
                      challenging because neurons are post-mitotic and cannot be
                      expanded for implementation in HTS. Therefore, HTS for
                      neuroprotective compounds requires a cell type that is
                      robustly expandable and able to differentiate into all of
                      the neuronal subtypes involved in disease pathogenesis.
                      Here, we report the derivation and propagation using only
                      small molecules of human neural progenitor cells (small
                      molecule neural precursor cells; smNPCs). smNPCs are robust,
                      exhibit immortal expansion, and do not require cumbersome
                      manual culture and selection steps. We demonstrate that
                      smNPCs have the potential to clonally and efficiently
                      differentiate into neural tube lineages, including motor
                      neurons (MNs) and midbrain dopaminergic neurons (mDANs) as
                      well as neural crest lineages, including peripheral neurons
                      and mesenchymal cells. These properties are so far only
                      matched by pluripotent stem cells. Finally, to demonstrate
                      the usefulness of smNPCs we show that mDANs differentiated
                      from smNPCs with LRRK2 G2019S are more susceptible to
                      apoptosis in the presence of oxidative stress compared to
                      wild-type. Therefore, smNPCs are a powerful biological tool
                      with properties that are optimal for large-scale disease
                      modeling, phenotypic screening, and studies of early human
                      development.},
      keywords     = {Cell Differentiation: genetics / Cell Differentiation:
                      physiology / Cells, Cultured / Electrophysiology /
                      Epithelial Cells: cytology / Epithelial Cells: metabolism /
                      Humans / Leucine-Rich Repeat Serine-Threonine Protein
                      Kinase-2 / Motor Neurons: cytology / Motor Neurons:
                      metabolism / Neural Crest: cytology / Neural Crest:
                      metabolism / Neural Stem Cells: cytology / Neural Stem
                      Cells: metabolism / Neurodegenerative Diseases: genetics /
                      Neurodegenerative Diseases: metabolism / Neurons: cytology /
                      Neurons: metabolism / Protein-Serine-Threonine Kinases:
                      genetics / Protein-Serine-Threonine Kinases: metabolism /
                      LRRK2 protein, human (NLM Chemicals) / Leucine-Rich Repeat
                      Serine-Threonine Protein Kinase-2 (NLM Chemicals) /
                      Protein-Serine-Threonine Kinases (NLM Chemicals)},
      cin          = {Zebrafish Models ; AG Schmid ; AG Schmid München / AG
                      Gasser 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1140002 / I:(DE-2719)1210000},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342) / 345
                      - Population Studies and Genetics (POF3-345)},
      pid          = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-345},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:23533608},
      pmc          = {pmc:PMC3606479},
      doi          = {10.1371/journal.pone.0059252},
      url          = {https://pub.dzne.de/record/136849},
}