title: Multiparametric Phenotypic Screening System for Profiling Bioactive Compounds Using Human Fetal Hippocampal Neural Stem/Progenitor Cells.
abstract: Stem cell research has been progressing rapidly, contributing to regenerative biology and regenerative medicine. In this field, small-molecule compounds affecting stem cell proliferation/differentiation have been explored to understand stem cell biology and support regenerative medicine. In this study, we established a multiparametric screening system to detect bioactive compounds affecting the cell fate of human neural stem/progenitor cells (NSCs/NPCs), using human fetal hippocampal NSCs/NPCs, HIP-009 cells. We examined effects of 410 compounds, which were collected based on mechanisms of action (MOAs) and chemotypes, on HIP-009's cell fate (self-renewal, neuronal and astrocytic differentiation) and morphology by automated multiparametric assays and profiled induced cellular phenotypes. We found that this screening classified compounds with the same MOAs into subgroups according to additional pharmacological effects (e.g., mammalian target of rapamycin complex 1 [mTORC1] inhibitors and mTORC1/mTORC2 dual inhibitors among mTOR inhibitors). Moreover, it identified compounds that have off-target effects under matrix analyses of MOAs and structure similarities (e.g., neurotropic effects of amitriptyline among tri- and tetracyclic compounds). Therefore, this automated, medium-throughput and multiparametric screening system is useful for finding compounds that affect the cell fate of human NSCs/NPCs for supporting regenerative medicine and to fingerprint compounds based on human stem cells' multipotency, leading to understanding of stem cell biology.
authors.affiliation: Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Murai
authors.affiliation: Global Discovery Research, Neuroscience and General Medicine PCU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan k5-yamazaki@hhc.eisai.co.jp.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ito
mesh_terms: D001681:Biological Assay; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D000066673:Cell Self Renewal / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology; D010641:Phenotype
chemical_list: D018491:Dopamine Agonists
keywords: bioactive compound library; cell fate; fingerprinting; human neural stem/progenitor cells; multiparametric phenotypic screening