Home > Publications Database > Derivation and expansion using only small molecules of human neural progenitors for neurodegenerative disease modeling. > print

001     136849
005     20240321220139.0
024 7 _ |a 10.1371/journal.pone.0059252
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024 7 _ |a pmid:23533608
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024 7 _ |a pmc:PMC3606479
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037 _ _ |a DZNE-2020-03171
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Reinhardt, Peter
|0 P:(DE-HGF)0
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245 _ _ |a Derivation and expansion using only small molecules of human neural progenitors for neurodegenerative disease modeling.
260 _ _ |a San Francisco, California, US
|c 2013
|b PLOS
264 _ 1 |3 online
|2 Crossref
|b Public Library of Science (PLoS)
|c 2013-03-22
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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536 _ _ |a 345 - Population Studies and Genetics (POF3-345)
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542 _ _ |i 2013-03-22
|2 Crossref
|u http://creativecommons.org/licenses/by/4.0/
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a LRRK2 protein, human
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a Protein-Serine-Threonine Kinases
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 2 |a Cell Differentiation: genetics
|2 MeSH
650 _ 2 |a Cell Differentiation: physiology
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Electrophysiology
|2 MeSH
650 _ 2 |a Epithelial Cells: cytology
|2 MeSH
650 _ 2 |a Epithelial Cells: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
|2 MeSH
650 _ 2 |a Motor Neurons: cytology
|2 MeSH
650 _ 2 |a Motor Neurons: metabolism
|2 MeSH
650 _ 2 |a Neural Crest: cytology
|2 MeSH
650 _ 2 |a Neural Crest: metabolism
|2 MeSH
650 _ 2 |a Neural Stem Cells: cytology
|2 MeSH
650 _ 2 |a Neural Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Neurodegenerative Diseases: genetics
|2 MeSH
650 _ 2 |a Neurodegenerative Diseases: metabolism
|2 MeSH
650 _ 2 |a Neurons: cytology
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Protein-Serine-Threonine Kinases: genetics
|2 MeSH
650 _ 2 |a Protein-Serine-Threonine Kinases: metabolism
|2 MeSH
700 1 _ |a Glatza, Michael
|0 P:(DE-HGF)0
|b 1
700 1 _ |a Hemmer, Kathrin
|0 P:(DE-HGF)0
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700 1 _ |a Tsytsyura, Yaroslav
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700 1 _ |a Thiel, Cora S
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700 1 _ |a Höing, Susanne
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700 1 _ |a Moritz, Sören
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700 1 _ |a Parga, Juan A
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700 1 _ |a Wagner, Lydia
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700 1 _ |a Bruder, Jan M
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700 1 _ |a Wu, Guangming
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700 1 _ |a Schmid, Benjamin
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700 1 _ |a Röpke, Albrecht
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700 1 _ |a Klingauf, Jürgen
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700 1 _ |a Schwamborn, Jens C
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700 1 _ |a Gasser, Thomas
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700 1 _ |a Schöler, Hans R
|0 P:(DE-HGF)0
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|e Corresponding author
700 1 _ |a Sterneckert, Jared
|0 P:(DE-HGF)0
|b 17
773 1 8 |a 10.1371/journal.pone.0059252
|b : Public Library of Science (PLoS), 2013-03-22
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773 _ _ |a 10.1371/journal.pone.0059252
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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913 1 _ |a DE-HGF
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914 1 _ |y 2013
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