Tagger-A Swiss army knife for multiomics to dissect cell type-specific mechanisms of gene expression in mice

• Published in: PLoS biology 2019-08, Vol.17 (8), p.e3000374-e3000374
• Main Authors: Kaczmarczyk, Lech, Bansal, Vikas, Rajput, Ashish, Rahman, Raza-Ur, Krzyżak, Wiesław, Degen, Joachim, Poll, Stefanie, Fuhrmann, Martin, Bonn, Stefan, Jackson, Walker Scot
• Format: Article
• Language: English
• Subjects: Acids; Animals; Biology; Biology and life sciences; Cloning, Molecular - methods; Funding; Gene expression; Gene Expression - genetics; Gene Expression Profiling - methods; Gene Expression Regulation - genetics; Gene Knock-In Techniques; Genetic regulation; Genetically modified mice; Genomics - methods; Medicine; Methods; Methods and Resources; Mice; Mice, Inbred C57BL; Mice, Transgenic - genetics; MicroRNAs; MicroRNAs - genetics; miRNA; Neurosciences; Nucleic acids; Nucleic Acids - isolation & purification; Phenotypes; Proteins; Proteomics - methods; Research and analysis methods; Ribonucleic acid; RNA; RNA sequencing; RNA, Messenger - genetics; Software; Stem cells; Supervision; Transcriptome - genetics; Transgenes - genetics; Transgenic mice; Whole Genome Sequencing - methods
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000374

A deep understanding of how regulation of the multiple levels of gene expression in mammalian tissues give rise to complex phenotypes has been impeded by cellular diversity. A handful of techniques were developed to tag-select nucleic acids of interest in specific cell types, thereby enabling their capture. We expanded this strategy by developing the Tagger knock-in mouse line bearing a quad-cistronic transgene combining enrichment tools for nuclei, nascent RNA, translating mRNA, and mature microRNA (miRNA). We demonstrate that Tagger can capture the desired nucleic acids, enabling multiple omics approaches to be applied to specific cell types in vivo using a single transgenic mouse line.