在这里，研究小组介绍了PEtracer的设计、开发和广泛验证，这是一种基于初始编辑的、不断发展的谱系追踪技术，与单细胞测序和多模态成像方法兼容，可以在分离细胞中联合描述细胞状态和谱系，同时在高空间分辨率的组织中保留细胞背景。利用PEtracer和MERFISH空间转录组分析在肿瘤转移的同基因motheme模型中，小组重建了个体种子肿瘤在体内的生长，并揭示了协调肿瘤生长的细胞内在和细胞外在因素的不同模块。更一般地说，PEtracer能够在生物相关的时间和空间尺度上系统地表征完整组织中的细胞状态和谱系关系。
据介绍，绘制发育和疾病中细胞命运决定的时空动态图是生物学中一个长期存在的目标。
附：英文原文
Title: High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer
Author: Luke W. Koblan, Kathryn E. Yost, Pu Zheng, William N. Colgan, Matthew G. Jones, Dian Yang, Arhan Kumar, Jaspreet Sandhu, Alexandra Schnell, Dawei Sun, Can Ergen, Reuben A. Saunders, Xiaowei Zhuang, William E. Allen, Nir Yosef, Jonathan S. Weissman
Issue&Volume: 2025-07-24
Abstract: Charting the spatiotemporal dynamics of cell fate determination in development and disease is a long-standing objective in biology. Here we present the design, development, and extensive validation of PEtracer, a prime editing-based, evolving lineage tracing technology compatible with both single-cell sequencing and multimodal imaging methodologies to jointly profile cell state and lineage in dissociated cells or while preserving cellular context in tissues with high spatial resolution. Using PEtracer coupled with MERFISH spatial transcriptomic profiling in a syngeneic mouse model of tumor metastasis, we reconstruct the growth of individually-seeded tumors in vivo and uncover distinct modules of cell-intrinsic and cell-extrinsic factors that coordinate tumor growth. More generally, PEtracer enables systematic characterization of cell state and lineage relationships in intact tissues over biologically-relevant temporal and spatial scales.
DOI: adx3800
Source: https://www.science.org/doi/10.1126/science.adx3800