Live-cell screening platform using human-induced pluripotent stem cells expressing fluorescence-tagged cytochrome P450 1A1
DC Field | Value | Language |
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dc.contributor.author | Kim, Ji-Woo | - |
dc.contributor.author | Im, Ilkyun | - |
dc.contributor.author | Kim, Hyemin | - |
dc.contributor.author | Jeon, Jang Su | - |
dc.contributor.author | Kang, Eun-Hye | - |
dc.contributor.author | Jo, Seongyea | - |
dc.contributor.author | Chun, Hang-Suk | - |
dc.contributor.author | Yoon, Seokjoo | - |
dc.contributor.author | Kim, Jong-Hoon | - |
dc.contributor.author | Kim, Sang Kyum | - |
dc.contributor.author | Park, Han-Jin | - |
dc.date.accessioned | 2021-08-30T20:26:07Z | - |
dc.date.available | 2021-08-30T20:26:07Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2020-07 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/54887 | - |
dc.description.abstract | Human-induced pluripotent stem cells (hiPSCs) are invaluable sources for drug screening and toxicity tests because of their differentiation potential and proliferative capacity. Recently, the CRISPR-Cas9-mediated homologous recombination system has enabled reporter knock-ins at desired loci in hiPSCs, and here, we generated a hiPSC reporter line expressing mCherry-tagged cytochrome P450 1A1 (CYP1A1), which can be utilized to screen for the modulators of aryl hydrocarbon receptor (AHR) in live cells. CYP1A1-mCherry hiPSCs exhibited typical characteristics of pluripotent stem cells such as marker expression, differentiation potential, and normal karyotype. After differentiation into hepatocyte-like cells (HLCs), CYP1A1-mCherry fusion protein was expressed and localized at the endoplasmic reticulum, and induced by AHR agonists. We obtained 23 hits modulating CYP1A1 expression from high-content screening with 241 hepatotoxicity chemicals and nuclear receptor ligands, and identified three upregulating chemicals and two downregulating compounds. Responses of hiPSC-HLCs against an AHR agonist were more similar to human primary hepatocytes than of HepG2 hepatocellular carcinoma cells. This platform has the advantages of live-cell screening without sacrificing cells (unlike previously available CYP1A1 reporter cell lines), as well as an indefinite supply of cells, and can be utilized in a wide range of screening related to AHR- and CYP1A1-associated diseases in desired cell types. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.subject | ARYL-HYDROCARBON RECEPTOR | - |
dc.subject | KNOCKOUT MOUSE LINES | - |
dc.subject | AH RECEPTOR | - |
dc.subject | GENE | - |
dc.subject | CANCER | - |
dc.subject | CYP1A1 | - |
dc.subject | POLYMORPHISMS | - |
dc.subject | INDUCTION | - |
dc.subject | PROTEINS | - |
dc.subject | LIGAND | - |
dc.title | Live-cell screening platform using human-induced pluripotent stem cells expressing fluorescence-tagged cytochrome P450 1A1 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Jong-Hoon | - |
dc.identifier.doi | 10.1096/fj.201903110R | - |
dc.identifier.scopusid | 2-s2.0-85084827400 | - |
dc.identifier.wosid | 000533521800001 | - |
dc.identifier.bibliographicCitation | FASEB JOURNAL, v.34, no.7, pp.9141 - 9155 | - |
dc.relation.isPartOf | FASEB JOURNAL | - |
dc.citation.title | FASEB JOURNAL | - |
dc.citation.volume | 34 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 9141 | - |
dc.citation.endPage | 9155 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Life Sciences & Biomedicine - Other Topics | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | ARYL-HYDROCARBON RECEPTOR | - |
dc.subject.keywordPlus | KNOCKOUT MOUSE LINES | - |
dc.subject.keywordPlus | AH RECEPTOR | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | CYP1A1 | - |
dc.subject.keywordPlus | POLYMORPHISMS | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | LIGAND | - |
dc.subject.keywordAuthor | AHR | - |
dc.subject.keywordAuthor | CRISPR-Cas9 | - |
dc.subject.keywordAuthor | high-content screening | - |
dc.subject.keywordAuthor | toxicology | - |
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