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Peer-reviewedCC BYCell stem cell

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

4 affiliations
  1. 1Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China
  2. 2CAS CEMCS-CUHK Joint Laboratory, New Cornerstone Science Laboratory, Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
  3. 3Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China
  4. 4Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang, China; School of Science, Westlake University, Hangzhou 310024, Zhejiang, China; Center for Interdisciplinary Studies, Westlake University, Hangzhou 310024, Zhejiang, China. Electronic address: [email protected]

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.

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BibTeX
@article{kang2026evolving,
  title = {{Evolving strategies for lineage tracing: Genetic markers, synthetic barcodes, and natural variants}},
  author = {Zhixin Kang and Hui Chen and Siyang Li and Shou‐Wen Wang and Bin Zhou},
  journal = {Cell stem cell},
  year = {2026},
  month = may,
  doi = {10.1016/j.stem.2026.05.001},
  url = {https://doi.org/10.1016/j.stem.2026.05.001},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Evolving strategies for lineage tracing: Genetic markers, synthetic barcodes, and natural variants
AU  - Zhixin Kang
AU  - Hui Chen
AU  - Siyang Li
AU  - Shou‐Wen Wang
AU  - Bin Zhou
PY  - 2026
DA  - 2026/05/29
JO  - Cell stem cell
DO  - 10.1016/j.stem.2026.05.001
UR  - https://doi.org/10.1016/j.stem.2026.05.001
AB  - 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.
SN  - 1875-9777
SN  - 1934-5909
ER  -