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细胞条形码与新一代谱系示踪技术的概念及应用

张婉莹, 裴唯珂^*

西湖大学生命科学学院，杭州 310024

摘要

谱系示踪(lineage tracing)是解析细胞命运和发育进程的核心技术。近年来，随着高通量测序与单细胞测序技术(single-cell sequencing)的发展，基于细胞条形码(cellular barcoding)的谱系示踪技术实现了从低通量向高分辨率、多维度解析的跨越。本文系统介绍了四类细胞条形码技术：基于病毒整合、转座子整合的随机DNA条形码、基于Cre-loxP 重组酶的遗传重排条形码，以及基于CRISPR-Cas9 的累积突变条形码；并分别阐述其原理和技术优势。此外，本文总结了当前技术在编辑精准性、时空信息整合及非侵入性示踪等方面面临的技术瓶颈，并重点讨论了先导编辑(prime editing)、时序记录系统、空间谱系示踪等领域前沿进展。总结来说，单细胞谱系示踪技术正由克隆标记向多模态信息整合方向发展，通过精准基因编辑工具与高分辨时空组学技术的深度融合，有望实现对细胞命运轨迹的动态、系统性解析，从而为发育生物学与再生医学提供关键技术工具。

关键词： 细胞条形码; 谱系示踪; 单细胞测序; 病毒整合; Cre-loxP重组酶; CRISPR-Cas9编辑

Cellular barcoding and next-generation lineage tracing: concepts and applications

ZHANG Wan-Ying, PEI Wei-Ke^*

School of Life Sciences, Westlake University, Hangzhou 310024, China

Abstract

Lineage tracing is a fundamental technique for dissecting cell fate decisions and development process. With recent advances in high-throughput sequencing and single-cell sequencing technologies, cellular barcoding-based lineage tracing strategies have transitioned from low-throughput labeling methods to high-resolution, multidimensional lineage reconstruction. In this review, we systematically summarize four major barcoding paradigms: viral integration-based random integration barcodes, transposon-based random integration barcodes, recombinase-mediated DNA rearrangement (e.g., Cre-loxP), and CRISPR-Cas9-based mutation recording systems. We describe their principles, representative studies, technical advantages, and limitations. Furthermore, we discuss the core bottlenecks in terms of editing precision, integration of spatiotemporal information, and non-invasive lineage tracing, with a focus on cutting-edge advancements such as prime editing, sequential recording systems, strategies for integrating spatial transcriptomics, and epigenetic tracing. Overall, single-cell lineage tracing is evolving from clonal labeling toward the multi-dimensional integration of lineage, state, and space. In the future, the deep integration of precise gene-editing tools with high-resolution spatial omics technologies is expected to enable dynamic and systematic analysis of cellular fate trajectories, thereby providing critical technical support for research in developmental biology and regenerative medicine.

Key words: cellular barcoding; lineage tracing; single-cell sequencing; viral integration; Cre-loxP recombinase; CRISPR-Cas9 edi

收稿日期：　　录用日期：

通讯作者：裴唯珂　　E-mail:

DOI: 10.13294/j.aps.2026.0063

引用本文：

张婉莹, 裴唯珂. 细胞条形码与新一代谱系示踪技术的概念及应用[J]. 生理学报 2026; 78 (4): 731-740.

ZHANG Wan-Ying, PEI Wei-Ke. Cellular barcoding and next-generation lineage tracing: concepts and applications. Acta Physiol Sin 2026; 78 (4): 731-740 (in Chinese with English abstract).