小柯机器人

美国加州大学Jonathan S. Weissman、Nir Yosef和麻省理工学院Tyler Jacks研究组，合作利用谱系追踪技术揭示了肿瘤进化的系统动力学、可塑性和路径。2022年5月5日出版的《细胞》发表了这项成果。

研究人员将基于单细胞RNA-seq读数的进化谱系示踪系统引入Kras;Trp53(KP)诱导的肺腺癌小鼠模型，并以前所未有的分辨率跟踪肿瘤从单转化细胞到转移性肿瘤的演变。研究发现，初始、稳定肺泡2型状态的丧失伴随着可塑性的短暂增加。随后采用不同的转录程序，这些程序能够实现快速扩增，并最终产生能够转移的稳定亚克隆。最后，肿瘤通过固定的进化轨迹进展，干扰其它肿瘤抑制因子以及创造新的进化轨迹来加速进展。

该研究阐明了肿瘤进化的层次结构，有利于对肿瘤进展进行深入研究。

据介绍，肿瘤进化是由逐渐获得的遗传和表观遗传改变造成的，这些改变使不受控的生长扩展到邻近和远端组织。对癌细胞之间系统发育关系的研究为理解这些过程提供了重要见解。

附：英文原文

Title: Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution

Author: Dian Yang, Matthew G. Jones, Santiago Naranjo, William M. Rideout, Kyung Hoi (Joseph) Min, Raymond Ho, Wei Wu, Joseph M. Replogle, Jennifer L. Page, Jeffrey J. Quinn, Felix Horns, Xiaojie Qiu, Michael Z. Chen, William A. Freed-Pastor, Christopher S. McGinnis, David M. Patterson, Zev J. Gartner, Eric D. Chow, Trever G. Bivona, Michelle M. Chan, Nir Yosef, Tyler Jacks, Jonathan S. Weissman

Issue&Volume: 2022-05-05

Abstract: Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct transcriptional programs that enable rapid expansion and, ultimately, clonal sweep of stable subclones capable of metastasizing. Finally, tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates progression by creating novel trajectories. Our study elucidates the hierarchical nature of tumor evolution and, more broadly, enables in-depth studies of tumor progression.

DOI: 10.1016/j.cell.2022.04.015

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00462-7