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DOI10.1126/science.aax6234
Massively multiplex chemical transcriptomics at single-cell resolution
Srivatsan S.R.; McFaline-Figueroa J.L.; Ramani V.; Saunders L.; Cao J.; Packer J.; Pliner H.A.; Jackson D.L.; Daza R.M.; Christiansen L.; Zhang F.; Steemers F.; Shendure J.; Trapnell C.
发表日期2020
ISSN0036-8075
起始页码45
结束页码51
卷号367期号:6473
英文摘要High-throughput chemical screens typically use coarse assays such as cell survival, limiting what can be learned about mechanisms of action, off-target effects, and heterogeneous responses. Here, we introduce “sci-Plex,” which uses “nuclear hashing” to quantify global transcriptional responses to thousands of independent perturbations at single-cell resolution. As a proof of concept, we applied sci-Plex to screen three cancer cell lines exposed to 188 compounds. In total, we profiled ~650,000 single-cell transcriptomes across ~5000 independent samples in one experiment. Our results reveal substantial intercellular heterogeneity in response to specific compounds, commonalities in response to families of compounds, and insight into differential properties within families. In particular, our results with histone deacetylase inhibitors support the view that chromatin acts as an important reservoir of acetate in cancer cells. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词4 (2 aminoethylamino) 1,8 dimethylimidazo[1,2 a]quinoxalineabexinostatacetic acidbelinostatcudc 101fimepinostatgivinostathistone deacetylase inhibitorm 344n [2 [3 (1 piperazinylmethyl)imidazo[2,1 b]thiazol 6 yl]phenyl] 2 quinoxalinecarboxamidepanobinostatpracinostatrec 2282trametinibtranscriptometrichostatin Aunclassified drugtranscriptomecancercellchemical analysisdetection methodexperimental studygenetic analysisresolutionA-549 cell lineanimal cellanimal experimentArticlecell functioncell heterogeneitycell labelingcell proliferationchromatincontrolled studydose responsedrug activityexperimentationgene controlgenetic transcriptionhumanhuman cellK-562 cell lineMCF-7 cell linemousenonhumanpilot studypriority journalproof of conceptRNA sequencescreeningsingle cell analysistranscriptomicscell nucleusdrug effectgeneticsgenomicshigh throughput screeningmetabolismneoplasmproceduressingle cell analysisA549 CellsAcetatesCell NucleusChromatinGenomicsHigh-Throughput Screening AssaysHistone Deacetylase InhibitorsHumansK562 CellsMCF-7 CellsNeoplasmsRNA-SeqSingle-Cell AnalysisTranscriptome
语种英语
来源机构Science
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/133804
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Srivatsan S.R.,McFaline-Figueroa J.L.,Ramani V.,et al. Massively multiplex chemical transcriptomics at single-cell resolution[J]. Science,2020,367(6473).
APA Srivatsan S.R..,McFaline-Figueroa J.L..,Ramani V..,Saunders L..,Cao J..,...&Trapnell C..(2020).Massively multiplex chemical transcriptomics at single-cell resolution.,367(6473).
MLA Srivatsan S.R.,et al."Massively multiplex chemical transcriptomics at single-cell resolution".367.6473(2020).
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