• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

重建结直肠癌中单细胞核型改变，鉴定出突发和逐渐多样化的模式。

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

机构信息

Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Oncode Institute, Utrecht, the Netherlands.

出版信息

Nat Genet. 2021 Aug;53(8):1187-1195. doi: 10.1038/s41588-021-00891-2. Epub 2021 Jul 1.

DOI:10.1038/s41588-021-00891-2
PMID:34211178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8346364/
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.

摘要

肿瘤进化的核心是遗传多样性的产生。然而，新的核型改变在人类肿瘤中出现和传播的程度和模式尚不清楚，特别是在单细胞分辨率下。在这里，我们提出了一种 3D Live-Seq-a 方案，该方案将肿瘤类器官生长的活细胞成像与每个成像细胞的全基因组测序相结合，以重建连续细胞代中不断进化的肿瘤细胞核型。使用源自患者的结直肠癌细胞类器官和新鲜肿瘤活检，我们证明了不同复杂程度的核型改变很常见，并且可以在几个细胞代内出现。亚染色体无着丝粒片段易于在连续细胞分裂中复制和集体错误分离。相比之下，大量全基因组的核型改变是在一个错误的细胞分裂中产生的，这为非整倍体肿瘤基因组可以通过间断进化来进化提供了支持。对癌症中核型多样化的时间动态和模式进行映射，可以重建向恶性适应性进化的路径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/393fc15cd8e1/41588_2021_891_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/ffb3ab295b3a/41588_2021_891_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/8c2f58c32207/41588_2021_891_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/d815a922030a/41588_2021_891_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/4820f26eff93/41588_2021_891_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/87aea908aaa7/41588_2021_891_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/c164b3cead8c/41588_2021_891_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/debe5d86a8b7/41588_2021_891_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/91485ee239ed/41588_2021_891_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/be5a3c5734c6/41588_2021_891_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/af56002e0a32/41588_2021_891_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/a1a09258ee82/41588_2021_891_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/e66d68bbe2dc/41588_2021_891_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/1ed3ec12ef73/41588_2021_891_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/1cf9a1f627ee/41588_2021_891_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/e25451e27e22/41588_2021_891_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/393fc15cd8e1/41588_2021_891_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/ffb3ab295b3a/41588_2021_891_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/8c2f58c32207/41588_2021_891_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/d815a922030a/41588_2021_891_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/4820f26eff93/41588_2021_891_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/87aea908aaa7/41588_2021_891_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/c164b3cead8c/41588_2021_891_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/debe5d86a8b7/41588_2021_891_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/91485ee239ed/41588_2021_891_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/be5a3c5734c6/41588_2021_891_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/af56002e0a32/41588_2021_891_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/a1a09258ee82/41588_2021_891_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/e66d68bbe2dc/41588_2021_891_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/1ed3ec12ef73/41588_2021_891_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/1cf9a1f627ee/41588_2021_891_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/e25451e27e22/41588_2021_891_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba8/8346364/393fc15cd8e1/41588_2021_891_Fig16_ESM.jpg

相似文献

1
Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns.重建结直肠癌中单细胞核型改变，鉴定出突发和逐渐多样化的模式。
Nat Genet. 2021 Aug;53(8):1187-1195. doi: 10.1038/s41588-021-00891-2. Epub 2021 Jul 1.
2
Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids.人类结直肠癌细胞类器官中的持续染色体不稳定性和核型演化。
Nat Genet. 2019 May;51(5):824-834. doi: 10.1038/s41588-019-0399-6. Epub 2019 Apr 29.
3
Rapid proliferation of daughter cells lacking particular chromosomes due to multipolar mitosis promotes clonal evolution in colorectal cancer cells.由于多极有丝分裂导致缺乏特定染色体的子细胞快速增殖，促进了结直肠癌细胞的克隆进化。
Cell Cycle. 2012 Jul 15;11(14):2650-9. doi: 10.4161/cc.20976.
4
A Markov chain for numerical chromosomal instability in clonally expanding populations.用于克隆扩展群体中数值染色体不稳定性的马尔可夫链。
PLoS Comput Biol. 2018 Sep 11;14(9):e1006447. doi: 10.1371/journal.pcbi.1006447. eCollection 2018 Sep.
5
Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes.特定非整倍体细胞的增殖优势驱动肿瘤核型的进化。
Biophys J. 2023 Feb 21;122(4):632-645. doi: 10.1016/j.bpj.2023.01.017. Epub 2023 Jan 18.
6
Single-cell RNA sequencing and machine learning provide candidate drugs against drug-tolerant persister cells in colorectal cancer.单细胞RNA测序和机器学习为治疗结直肠癌中的耐药性持久性细胞提供了候选药物。
Biochim Biophys Acta Mol Basis Dis. 2025 Mar;1871(3):167693. doi: 10.1016/j.bbadis.2025.167693. Epub 2025 Jan 25.
7
The evolution of single cell-derived colorectal cancer cell lines is dominated by the continued selection of tumor-specific genomic imbalances, despite random chromosomal instability.单细胞衍生的结直肠癌细胞系的进化主要由肿瘤特异性基因组失衡的持续选择所主导，尽管存在随机染色体不稳定性。
Carcinogenesis. 2018 Jul 30;39(8):993-1005. doi: 10.1093/carcin/bgy068.
8
Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases.从人类结直肠癌转移灶活检样本培养的类器官中保留的遗传多样性。
Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13308-11. doi: 10.1073/pnas.1516689112. Epub 2015 Oct 12.
9
Intra-tumour diversification in colorectal cancer at the single-cell level.单细胞水平的结直肠癌肿瘤内多样化。
Nature. 2018 Apr;556(7702):457-462. doi: 10.1038/s41586-018-0024-3. Epub 2018 Apr 11.
10
Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.通过选择特定的非整倍体来适应纺锤体组装检验点抑制。
Genes Dev. 2023 Mar 1;37(5-6):171-190. doi: 10.1101/gad.350182.122.

引用本文的文献

1
Ongoing genome doubling shapes evolvability and immunity in ovarian cancer.持续的基因组加倍塑造了卵巢癌的进化能力和免疫特性。
Nature. 2025 Jul 16. doi: 10.1038/s41586-025-09240-3.
2
Development and validation of an MRI spatiotemporal interaction model for early noninvasive prediction of neoadjuvant chemotherapy response in breast cancer: a multicentre study.用于乳腺癌新辅助化疗反应早期无创预测的MRI时空相互作用模型的开发与验证：一项多中心研究
EClinicalMedicine. 2025 Jun 12;85:103298. doi: 10.1016/j.eclinm.2025.103298. eCollection 2025 Jul.
3
High-throughput mapping of spontaneous mitotic crossover and genome instability events with sci-L3-Strand-seq.
利用sci-L3-Strand-seq对自发有丝分裂交换和基因组不稳定事件进行高通量定位。
bioRxiv. 2025 May 26:2025.05.19.654945. doi: 10.1101/2025.05.19.654945.
4
Cell-cycle dependent DNA repair and replication unifies patterns of chromosome instability.细胞周期依赖性DNA修复与复制统一了染色体不稳定模式。
Nat Commun. 2025 Mar 28;16(1):3033. doi: 10.1038/s41467-025-58245-z.
5
Colorectal Adenoma Subtypes Exhibit Signature Molecular Profiles: Unique Insights into the Microenvironment of Advanced Precancerous Lesions for Early Detection Applications.结直肠腺瘤亚型呈现出特征性分子图谱：对晚期癌前病变微环境的独特见解，用于早期检测应用。
Cancers (Basel). 2025 Feb 14;17(4):654. doi: 10.3390/cancers17040654.
6
Unravelling single-cell DNA replication timing dynamics using machine learning reveals heterogeneity in cancer progression.利用机器学习揭示单细胞DNA复制时间动态变化揭示癌症进展中的异质性。
Nat Commun. 2025 Feb 8;16(1):1472. doi: 10.1038/s41467-025-56783-0.
7
TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling.TRACERx分析确定了FAT1在通过Hippo信号通路调节染色体不稳定性和全基因组加倍过程中的作用。
Nat Cell Biol. 2025 Jan;27(1):154-168. doi: 10.1038/s41556-024-01558-w. Epub 2024 Dec 30.
8
Characterizing the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER.利用SPRINTER表征单细胞克隆中癌症增殖的进化动力学。
Nat Genet. 2025 Jan;57(1):103-114. doi: 10.1038/s41588-024-01989-z. Epub 2024 Nov 29.
9
Modeling epithelial-mesenchymal transition in patient-derived breast cancer organoids.在患者来源的乳腺癌类器官中模拟上皮-间质转化
Front Oncol. 2024 Oct 14;14:1470379. doi: 10.3389/fonc.2024.1470379. eCollection 2024.
10
Simple aneuploidy evades p53 surveillance and promotes niche factor-independent growth in human intestinal organoids.简单的非整倍体逃避了 p53 的监测，并促进了人类肠道类器官中龛因子非依赖性的生长。
Mol Biol Cell. 2024 Aug 1;35(8):br15. doi: 10.1091/mbc.E24-04-0166. Epub 2024 Jul 10.