Work

Evolving strategies for lineage tracing: Genetic markers, synthetic barcodes, and natural variants

Year: 2026

Type: review

Abstract: Elucidating cell fate decision-making requires linking lineage history to dynamic phenotypic states. Driven by single-cell sequencing and genome engineering, lineage tracing has evolved from observational studies into a multidimensional, high-throughput discipline. Here, we synthesize its three methodological pillars: prospective tracking via genetic markers, high-throughput mapping using synthetic barcodes, and retrospective tracing leveraging endogenous natural variants. We survey their integration with multi-omics and spatial profiling, alongside computational approaches to decode cell fates from lineage data. By detailing each approach's trade-offs, we offer a systematic guide for experimental design and highlight emerging frontiers for translating precision clonal analysis into the clinic.

Source: Cell stem cell

DOI: 10.1016/j.stem.2026.05.001

Authors: Zhixin Kang, Hui Chen, Siyang Li, Shou-Wen Wang, Bin Zhou

Institutions: University of Chinese Academy of Sciences, Chinese Academy of Sciences, Center for Excellence in Molecular Cell Science, Westlake University, ShanghaiTech University

Language: English

Topic: Single-cell and spatial transcriptomics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $10,400

Funders: National Natural Science Foundation of China, National Key Research and Development Program of China, Key Research and Development Program of Zhejiang Province