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dc.contributor.authorZhao, Wen-Ning
dc.contributor.authorCheng, Chialin
dc.contributor.authorTheriault, Kraig M.
dc.contributor.authorSheridan, Steven D.
dc.contributor.authorTsai, Li-Huei
dc.contributor.authorHaggarty, Stephen J.
dc.date.accessioned2015-01-15T18:40:55Z
dc.date.available2015-01-15T18:40:55Z
dc.date.issued2012-08
dc.date.submitted2012-05
dc.identifier.issn1087-0571
dc.identifier.issn1552-454X
dc.identifier.urihttp://hdl.handle.net/1721.1/92893
dc.description.abstractWnt/β-catenin signaling has emerged as a central player in pathways implicated in the pathophysiology and treatment of neuropsychiatric disorders. To identify potential novel therapeutics for these disorders, high-throughput screening (HTS) assays reporting on Wnt/β-catenin signaling in disease-relevant contexts are needed. The use of human patient–derived induced pluripotent stem cell (iPSC) models provides ideal disease-relevant context if these stem cell cultures can be adapted for HTS-compatible formats. Here, we describe a sensitive, HTS-compatible Wnt/β-catenin signaling reporter system generated in homogeneous, expandable neural progenitor cells (NPCs) derived from human iPSCs. We validated this system by demonstrating dose-responsive stimulation by several known Wnt/β-catenin signaling pathway modulators, including Wnt3a, a glycogen synthase kinase-3 (GSK3) inhibitor, and the bipolar disorder therapeutic lithium. These responses were robust and reproducible over time across many repeated assays. We then conducted a screen of ~1500 compounds from a library of Food and Drug Administration–approved drugs and known bioactives and confirmed the HTS hits, revealing multiple chemical and biological classes of novel small-molecule probes of Wnt/β-catenin signaling. Generating these type of pathway-selective, cell-based phenotypic assays in human iPSC-derived neural cells will advance the field of human experimental neurobiology toward the goal of identifying and validating targets for neuropsychiatric disorders.en_US
dc.description.sponsorshipNational Institute of Mental Health (U.S.) (Grant R01MH091115)en_US
dc.description.sponsorshipStanley Medical Research Instituteen_US
dc.language.isoen_US
dc.publisherSage Publicationsen_US
dc.relation.isversionofhttp://dx.doi.org/10.1177/1087057112456876en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleA High-Throughput Screen for Wnt/β-Catenin Signaling Pathway Modulators in Human iPSC-Derived Neural Progenitorsen_US
dc.typeArticleen_US
dc.identifier.citationZhao, Wen-Ning, Chialin Cheng, Kraig M. Theriault, Steven D. Sheridan, Li-Huei Tsai, and Stephen J. Haggarty. “A High-Throughput Screen for Wnt/β-Catenin Signaling Pathway Modulators in Human iPSC-Derived Neural Progenitors.” Journal of Biomolecular Screening 17, no. 9 (August 24, 2012): 1252–1263.en_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.mitauthorTsai, Li-Hueien_US
dc.relation.journalJournal of Biomolecular Screeningen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsZhao, Wen-Ning; Cheng, Chialin; Theriault, Kraig M.; Sheridan, Steven D.; Tsai, Li-Huei; Haggarty, Stephen J.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1262-0592
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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