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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},
}