LINNAEUS: Simultaneous Single-Cell Lineage Tracing and Cell Type Identification.

Area of Science:

• Cell biology
• Genomics
• Developmental biology

Background:

• Identifying cell types and their origins is fundamental to understanding biological processes like development, regeneration, and disease.
• Single-cell RNA sequencing (scRNA-seq) is a powerful tool for cell type identification but struggles with reconstructing lineage relationships.
• Organizing cell taxonomies into lineage trees to understand cell origins and relationships remains a significant challenge.

Purpose of the Study:

• To present LINNAEUS (LINeage tracing by Nuclease-Activated Editing of Ubiquitous Sequences), a novel strategy for simultaneous lineage tracing and transcriptome profiling.
• To enable the reconstruction of organism-wide single-cell lineage trees.
• To provide a systematic approach for tracing the origins of both novel and known cell types under various conditions.

Main Methods:

• LINNAEUS combines scRNA-seq with computational analysis of lineage barcodes.
• Lineage barcodes are generated through genome editing of transgenic reporter genes.
• This approach allows for the analysis of thousands of single cells simultaneously.

Main Results:

• LINNAEUS facilitates simultaneous lineage tracing and transcriptome profiling.
• The method enables the reconstruction of comprehensive single-cell lineage trees across an organism.
• It offers a systematic way to investigate cell origins and relationships.

Conclusions:

• LINNAEUS overcomes limitations in reconstructing cell lineages from scRNA-seq data.
• This strategy provides a powerful tool for studying cell fate and developmental processes.
• LINNAEUS advances our ability to understand cell origins in diverse biological contexts.