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A programmable sequence of reporters for lineage analysis
Jorge Garcia-Marques1, Isabel Espinosa-Medina2, Kai-Yuan Ku3
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. garciamarquesj@janelia.hhmi.org.
Nature Neuroscience
|July 29, 2020
Summary
We developed CLADES (cell lineage access driven by an edition sequence), a CRISPR-Cas9 tool for cell lineage tracing. This technology uses genetic switches to sequentially activate reporters, recording cell birth order and developmental events.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Cell lineage studies are crucial for understanding development and disease.
- Existing methods for lineage tracing often lack temporal resolution or scalability.
- CRISPR-Cas9 technology offers precise genome editing capabilities.
Purpose of the Study:
- To introduce CLADES, a novel technology for cell lineage tracing.
- To enable temporal resolution of cell lineage development using programmable gene cascades.
- To provide a method for recording serial biological events across generations.
Main Methods:
- CLADES utilizes CRISPR-Cas9 to control genetic switches for reporter gene activation.
- Reporter gene expression is sequentially activated in a predetermined order.
- The system can be temporally induced, for example, by heat shock.
- CLADES can be targeted to progenitor cells or the germ line.
Main Results:
- CLADES successfully couples cell birth order to sequential reporter gene expression in progeny.
- The system allows for the temporal deconstruction of extended cell lineages.
- When targeted to the germ line, CLADES marks successive animal generations with distinct reporter combinations.
- Programmable gene cascades for genetic manipulation or event recording were achieved.
Conclusions:
- CLADES provides an innovative strategy for cell lineage tracing with high temporal resolution.
- The technology enables the recording of biological events in a sequential and programmable manner.
- CLADES has potential applications in developmental biology, genetic manipulation, and understanding generational inheritance patterns.
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