Charting single-cell lineages with synthetic and natural barcodes

Area of Science:

• Cellular and Molecular Biology
• Developmental Biology
• Cancer Biology

Background:

• Cellular division and differentiation form organ structures throughout life.
• With aging and cancer, specific cell clones can dominate organismal fate.
• Phenotypic heterogeneity underlies diverse cellular functions like regeneration and stress response.

Purpose of the Study:

• To explore how single-cell lineage tracing reconstructs cellular ancestries.
• To re-evaluate established concepts in development, aging, and cancer biology.
• To understand the basis of phenotypic heterogeneity in cellular functions.

Main Methods:

• Utilizing synthetic and natural barcoding techniques for cellular ancestry reconstruction.
• Employing single-cell resolution for high-precision lineage tracing.
• Developing multimodal tracing methods integrating spatial, genetic, epigenetic, and transcriptomic data.

Main Results:

• Single-cell lineage tracing enables unprecedented resolution of cellular ancestries.
• These studies are reshaping fundamental understanding in development, aging, and cancer.
• Insights into phenotypic heterogeneity and its role in cellular functions are emerging.

Conclusions:

• Cellular lineage tracing is revolutionizing developmental, aging, and cancer research.
• Advancements in multimodal tracing are overcoming methodological challenges.
• Future clinical applications of clonal analysis may enhance disease detection, prediction, and prevention.