小柯机器人

荷兰乌得勒支大学Hugo J. G. Snippert课题组的研究通过结直肠癌单细胞核型重构，确定了肿瘤细胞进化的点状和逐渐多样化模式。相关论文于2021年7月1日发表在《自然-遗传学》杂志上。

研究人员研发了3D Live-Seq，这是一种将肿瘤类器官生长的活细胞成像和每个成像细胞的全基因组测序相结合的技术，以在细胞连续传代过程中重建不断发展的肿瘤细胞核型。使用源自结直肠癌患者的类器官和对新鲜肿瘤标本的活检，研究证明了不同复杂性的核型改变普遍存在，并且可以在几代细胞内出现。亚染色体无着丝粒片段易于在连续细胞分裂中复制和集中错误分离。

相比之下，在单个细胞分裂中产生的错误导致了严重的全基因组核型改变，这为非整倍体肿瘤基因组可通过间断进化提供了支持。通过绘制癌症核型多样化的时间动态和模式能够重建肿瘤细胞恶性发展的进化历程。

研究人员表示，肿瘤进化的核心是遗传多样性的产生。然而，对人类肿瘤中新生核型改变的出现时间、传播的程度和模式尚不清楚，尤其是在单细胞分辨率。

附：英文原文

Title: Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns

Author: Yannik Bollen, Ellen Stelloo, Petra van Leenen, Myrna van den Bos, Bas Ponsioen, Bingxin Lu, Markus J. van Roosmalen, Ana C. F. Bolhaqueiro, Christopher Kimberley, Maximilian Mossner, William C. H. Cross, Nicolle J. M. Besselink, Bastiaan van der Roest, Sander Boymans, Koen C. Oost, Sippe G. de Vries, Holger Rehmann, Edwin Cuppen, Susanne M. A. Lens, Geert J. P. L. Kops, Wigard P. Kloosterman, Leon W. M. M. Terstappen, Chris P. Barnes, Andrea Sottoriva, Trevor A. Graham, Hugo J. G. Snippert

Issue&Volume: 2021-07-01

Abstract: Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq—a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness.

DOI: 10.1038/s41588-021-00891-2

Source: https://www.nature.com/articles/s41588-021-00891-2

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex