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Related Experiment Video

Updated: Jun 28, 2025

Lineage Labeling of Zebrafish Cells with Laser Uncagable Fluorescein Dextran
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Achieving single-cell-resolution lineage tracing in zebrafish by continuous barcoding mutations during embryogenesis.

Zhan Liu1, Hui Zeng1, Huimin Xiang1

  • 1State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510275, China.

Journal of Genetics and Genomics = Yi Chuan Xue Bao
|April 15, 2024
PubMed
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This study introduces a high-resolution cell barcoding system for zebrafish, enabling detailed lineage tracing. The findings reveal that regenerated fin cells originate locally and highlight the early divergence of germ and somatic cells.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Zebrafish Model Organisms

Background:

  • Understanding cell lineage is crucial for developmental and stem cell biology.
  • Existing zebrafish cell barcoding methods lack sufficient resolution for embryogenesis.
  • The Substitution Mutation-Aided Lineage-Tracing system (SMALT) showed promise in Drosophila.

Purpose of the Study:

  • To implement and validate the SMALT system for high-resolution cell lineage tracing in zebrafish.
  • To reconstruct cell phylogenetic trees for zebrafish fin development and regeneration.
  • To investigate germ cell pool stability and germ-soma progenitor separation.

Main Methods:

  • Adaptation of the SMALT system for zebrafish embryos.
  • Recording substitution mutations in a barcoding sequence in one-day post-fertilization embryos.
Keywords:
Cellular barcodingFin regenerationGerm cell lineageLineage tracingZebrafish cell phylogeny

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  • Reconstruction of cell lineage trees using high-resolution phylogenetic analysis.

    • Main Results:

    • Achieved a median of 14 substitution mutations per kilobase pair, enabling detailed lineage reconstruction.
    • Reconstructed four high-support (median 99% bootstrap) cell lineage trees for zebrafish fin cells (original and regenerated).
    • Demonstrated that regenerated fin cells primarily arise from local progenitor cells.
    • Confirmed germ cell pool stability and early segregation of germ and somatic progenitors.

    Conclusions:

    • The SMALT system provides high-resolution lineage tracing in zebrafish, overcoming previous limitations.
    • Regenerated fin cells exhibit local origins, offering insights into tissue repair mechanisms.
    • The system is valuable for studying developmental processes, tissue regeneration, and disease in zebrafish.