Advances in CRISPR-Cas9 in lineage tracing of model animals

Jingchao Cao , Zihang Guo , Xueling Xu , Pan Li , Yi Fang , Shoulong Deng

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (6) : 1004 -1022.

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Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (6) : 1004 -1022. DOI: 10.1002/ame2.70033
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Advances in CRISPR-Cas9 in lineage tracing of model animals

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Abstract

Cell lineage tracing is a key technology for describing the developmental history of individual progenitor cells and assembling them to form a lineage development tree. However, traditional methods have limitations of poor stability and insufficient resolution. As an efficient and flexible gene editing tool, CRISPR-Cas9 system has been widely used in biological research. Furthermore, CRISPR-Cas9 gene editing-based tracing methods can introduce fluorescent proteins, reporter genes, or DNA barcodes for high-throughput sequencing, enabling precise lineage analysis, significantly improving precision and resolution, and expanding its application range. In this review, we summarize applications of CRISPR-Cas9 system in cell lineage tracing, with special emphasis on its successful applications in traditional model animals (e.g., zebrafish and mice), large animal models (pigs), and human cells or organoids. We also discussed its potential prospects and challenges in xenotransplantation and regenerative medicine.

Keywords

cell lineage tracing / CRISPR-Cas9 / DNA barcoding / high-throughput sequencing / xenotransplantation

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Jingchao Cao, Zihang Guo, Xueling Xu, Pan Li, Yi Fang, Shoulong Deng. Advances in CRISPR-Cas9 in lineage tracing of model animals. Animal Models and Experimental Medicine, 2025, 8(6): 1004-1022 DOI:10.1002/ame2.70033

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2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

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