Whole-organism clone tracing using single-cell sequencing

Area of Science:

• Developmental Biology
• Genomics
• Cell Biology

Background:

• Understanding how limited embryonic progenitors generate all adult cell types is crucial for developmental biology.
• Simultaneously measuring clonal history and cell identity at single-cell resolution has been a significant technical challenge.
• Existing methods for tracing clonal history are often indirect or lack single-cell resolution.

Purpose of the Study:

• To develop a single-cell sequencing strategy for simultaneous quantification of clonal history and cell type.
• To apply this strategy to map progenitor-derived cell types in adult zebrafish organs.
• To investigate progenitor commitment and cell fate decisions during embryonic development and regeneration.

Main Methods:

• Development of ScarTrace, a single-cell sequencing strategy.
• Application of ScarTrace to thousands of cells from various adult zebrafish organs.
• Analysis of clonal relationships and cell-type classification using transcriptomic data.

Main Results:

• Identified multipotent embryonic progenitors generating all hematopoietic cells in zebrafish kidney marrow.
• Demonstrated progenitor-specific cell type generation in eyes and brain, and studied eye laterality commitment.
• Revealed shared progenitors for epidermal and mesenchymal cells in caudal fins, and identified distinct clonal origins for resident immune cells.

Conclusions:

• ScarTrace enables simultaneous, high-resolution analysis of clonal history and cell identity.
• The study provides a detailed map of progenitor-derived cell types in adult zebrafish.
• This approach offers a powerful tool for reconstructing organismal development from single cells across various experimental systems.