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A multi-kingdom genetic barcoding system for precise clone isolation
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DOI：10.1038/s41587-025-02649-1.png)
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Abstract
En 中文
Cell-tagging strategies with DNA barcodes have enabled the analysis of clone size dynamics and clone-restricted transcriptomic landscapes in heterogeneous populations. However, isolating a target clone that displays a specific phenotype from a complex population remains challenging. Here we present a multi-kingdom genetic barcoding system, CloneSelect, which enables a target cell clone to be triggered to express a reporter gene for isolation through barcode-specific CRISPR base editing. In CloneSelect, cells are first stably tagged with DNA barcodes and propagated so that their subpopulation can be subjected to a given experiment. A clone that shows a phenotype or genotype of interest at a given time can then be isolated from the initial or subsequent cell pools stored during the experiment using CRISPR base editing. CloneSelect is scalable and compatible with single-cell RNA sequencing. We demonstrate the versatility of CloneSelect in human embryonic kidney 293T cells, mouse embryonic stem cells, human pluripotent stem cells, yeast cells and bacterial cells.
Keywords:
EPIGENETIC MEMORY
LINEAGE
CELLS
DIFFERENTIATION
DNA
ADAPTATION
INDUCTION
DYNAMICS
DESIGN
FATE
Journal
IF:
41.7
Papers:
1.2W
Citations:
10.1W
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