Control of Lineage-Specific Gene Expression by Functionalized gRNA Barcodes

ACS Synth Biol. 2018 Oct 19;7(10):2468-2474. doi: 10.1021/acssynbio.8b00105. Epub 2018 Sep 17.

Abstract

Lineage tracking delivers essential quantitative insight into dynamic, probabilistic cellular processes, such as somatic tumor evolution and differentiation. Methods for high diversity lineage quantitation rely on sequencing a population of DNA barcodes. However, manipulation of specific individual lineages is not possible with this approach. To address this challenge, we developed a functionalized lineage tracing tool, Control of Lineages by Barcode Enabled Recombinant Transcription (COLBERT), that enables high diversity lineage tracing and lineage-specific manipulation of gene expression. This modular platform utilizes expressed barcode gRNAs to both track cell lineages and direct lineage-specific gene expression.

Keywords: barcode; clonal dynamics; heterogeneity; lineage tracing; population variation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CRISPR-Associated Protein 9 / genetics
  • Cell Line, Tumor
  • Cell Lineage
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Lentivirus / physiology

Substances

  • CRISPR-Associated Protein 9