136849 20240321220139.0 10.1371/journal.pone.0059252 doi pmid:23533608 pmid pmc:PMC3606479 pmc altmetric:1318066 altmetric DZNE-2020-03171 English 610 Reinhardt, Peter P:(DE-HGF)0 0 Derivation and expansion using only small molecules of human neural progenitors for neurodegenerative disease modeling. San Francisco, California, US 2013 PLOS online Crossref Public Library of Science (PLoS) 2013-03-22 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1602248004_27532 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 345 - Population Studies and Genetics (POF3-345) G:(DE-HGF)POF3-345 POF3-345 POF III 1 2013-03-22 Crossref http://creativecommons.org/licenses/by/4.0/ Dataset connected to CrossRef, PubMed, LRRK2 protein, human EC 2.7.11.1 NLM Chemicals Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 EC 2.7.11.1 NLM Chemicals Protein-Serine-Threonine Kinases EC 2.7.11.1 NLM Chemicals Cell Differentiation: genetics MeSH Cell Differentiation: physiology MeSH Cells, Cultured MeSH Electrophysiology MeSH Epithelial Cells: cytology MeSH Epithelial Cells: metabolism MeSH Humans MeSH Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 MeSH Motor Neurons: cytology MeSH Motor Neurons: metabolism MeSH Neural Crest: cytology MeSH Neural Crest: metabolism MeSH Neural Stem Cells: cytology MeSH Neural Stem Cells: metabolism MeSH Neurodegenerative Diseases: genetics MeSH Neurodegenerative Diseases: metabolism MeSH Neurons: cytology MeSH Neurons: metabolism MeSH Protein-Serine-Threonine Kinases: genetics MeSH Protein-Serine-Threonine Kinases: metabolism MeSH Glatza, Michael P:(DE-HGF)0 1 Hemmer, Kathrin P:(DE-HGF)0 2 Tsytsyura, Yaroslav P:(DE-HGF)0 3 Thiel, Cora S P:(DE-HGF)0 4 Höing, Susanne P:(DE-HGF)0 5 Moritz, Sören P:(DE-HGF)0 6 Parga, Juan A P:(DE-HGF)0 7 Wagner, Lydia P:(DE-HGF)0 8 Bruder, Jan M P:(DE-HGF)0 9 Wu, Guangming P:(DE-HGF)0 10 Schmid, Benjamin P:(DE-2719)9000388 11 dzne Röpke, Albrecht P:(DE-HGF)0 12 Klingauf, Jürgen P:(DE-HGF)0 13 Schwamborn, Jens C P:(DE-HGF)0 14 Gasser, Thomas P:(DE-2719)2320009 15 dzne Schöler, Hans R P:(DE-HGF)0 16 Corresponding author Sterneckert, Jared P:(DE-HGF)0 17 10.1371/journal.pone.0059252 : Public Library of Science (PLoS), 2013-03-22 3 e59252 journal-article Crossref PLoS ONE 8 2013 1932-6203 10.1371/journal.pone.0059252 Vol. 8, no. 3, p. e59252 - PERI:(DE-600)2267670-3 3 8:3<e59252 - e59252 PLOS ONE 8 2013 1932-6203 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059252 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606479 http://pub.dzne.de/record/136849/files/3474.PDF OpenAccess http://pub.dzne.de/record/136849/files/3474.gif?subformat=icon icon OpenAccess http://pub.dzne.de/record/136849/files/3474.jpg?subformat=icon-1440 icon-1440 OpenAccess http://pub.dzne.de/record/136849/files/3474.jpg?subformat=icon-180 icon-180 OpenAccess http://pub.dzne.de/record/136849/files/3474.jpg?subformat=icon-640 icon-640 OpenAccess oai:pub.dzne.de:136849 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 11 P:(DE-2719)9000388 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 15 P:(DE-2719)2320009 DE-HGF Forschungsbereich Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3-300 Disease Mechanisms and Model Systems 0 DE-HGF Forschungsbereich Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-345 G:(DE-HGF)POF3-300 Population Studies and Genetics 1 2013 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search DBCoverage StatID:(DE-HGF)1040 StatID Zoological Record JCR StatID:(DE-HGF)0100 StatID PLOS ONE : 2017 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal DBCoverage StatID:(DE-HGF)0500 StatID DOAJ WoS StatID:(DE-HGF)0111 StatID Science Citation Index Expanded DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection IF < 5 StatID:(DE-HGF)9900 StatID OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC DBCoverage StatID:(DE-HGF)0310 StatID NCBI Molecular Biology Database DBCoverage StatID:(DE-HGF)0300 StatID Medline DBCoverage StatID:(DE-HGF)0320 StatID PubMed Central DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List I:(DE-2719)1140002 Zebrafish Models ; 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