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

PLoS Biol. 2019 Aug 8;17(8):e3000374. doi: 10.1371/journal.pbio.3000374. eCollection 2019 Aug.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cloning, Molecular / methods
  • Gene Expression / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation / genetics
  • Gene Knock-In Techniques
  • Genomics / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics
  • MicroRNAs / genetics
  • Nucleic Acids / isolation & purification*
  • Proteomics / methods
  • RNA, Messenger / genetics
  • Transcriptome / genetics
  • Transgenes / genetics
  • Whole Genome Sequencing / methods*

Substances

  • MicroRNAs
  • Nucleic Acids
  • RNA, Messenger

Grants and funding

This work was generously supported by internal funding from the Knut and Alice Wallenberg Foundation and the German Center for Neurodegenerative Diseases. Additionally, MF was supported by grants from the German Research Foundation (SFB 1089, C01, B06) and ERA-NET NEURON (MicroSynDep, MicroSchiz). VB, AR, RR, and SB were supported by DFG and BMBF (BO4221, IDSN, SFB 1286 Z2), Helmholtz iMed, and VW German-Israeli grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.