MaltSci 麦伴科研

Appearance

文献精选 > 高引权威"类器官"文献

Genetically engineered cerebral organoids model brain tumor formation. ​

文献信息 ​

DOI10.1038/s41592-018-0070-7
PMID30038414
期刊Nature methods
影响因子32.1
JCR 分区Q1
发表年份2018
被引次数212
关键词基因工程, 脑肿瘤, 类脑器官, 肿瘤生物学, CRISPR-Cas9
文献类型Journal Article, Research Support, Non-U.S. Gov't
ISSN1548-7091
页码631-639
期号15(8)
作者Shan Bian, Marko Repic, Zhenming Guo, Anoop Kavirayani, Thomas Burkard, Joshua A Bagley, Christian Krauditsch, Jürgen A Knoblich

一句话小结 ​

本研究开发了一种新生肿瘤性脑类器官（neoCOR）三维体外模型，以重现脑肿瘤的发生过程，并通过筛选临床相关突变定义导致类胶质母细胞瘤和CNS-PNET的突变组合。该模型为脑肿瘤生物学研究提供了新的工具，能够深入探索肿瘤的侵袭性和药物效果评估，具有重要的研究意义。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

基因工程 · 脑肿瘤 · 类脑器官 · 肿瘤生物学 · CRISPR-Cas9

摘要 ​

脑肿瘤是最致命和破坏性最大的癌症之一。其研究受到遗传异质性和现有实验室模型不完整性的限制。三维类器官培养模型为人类疾病建模提供了创新的可能性。在此，我们建立了一种称为新生肿瘤性脑类器官（neoCOR）的三维体外模型，通过转座子和CRISPR-Cas9介导的突变来在脑类器官中重现脑肿瘤发生过程。通过筛选在癌症基因组项目中识别的临床相关突变，我们定义了导致类胶质母细胞瘤和中枢神经系统原始神经外胚层肿瘤（CNS-PNET）样肿瘤的突变组合。我们证明了neoCOR适用于研究肿瘤生物学的各个方面，例如侵袭性，以及在特定DNA异常背景下评估药物效果。neoCOR将为当前用于研究脑肿瘤生物学的基础和临床前模型提供有价值的补充。

英文摘要 ​

Brain tumors are among the most lethal and devastating cancers. Their study is limited by genetic heterogeneity and the incompleteness of available laboratory models. Three-dimensional organoid culture models offer innovative possibilities for the modeling of human disease. Here we establish a 3D in vitro model called a neoplastic cerebral organoid (neoCOR), in which we recapitulate brain tumorigenesis by introducing oncogenic mutations in cerebral organoids via transposon- and CRISPR-Cas9-mediated mutagenesis. By screening clinically relevant mutations identified in cancer genome projects, we defined mutation combinations that result in glioblastoma-like and central nervous system primitive neuroectodermal tumor (CNS-PNET)-like neoplasms. We demonstrate that neoCORs are suitable for use in investigations of aspects of tumor biology such as invasiveness, and for evaluation of drug effects in the context of specific DNA aberrations. NeoCORs will provide a valuable complement to the current basic and preclinical models used to study brain tumor biology.

麦伴智能科研服务 ​

智能阅读回答你对文献的任何问题，帮助理解文献中的复杂图表和公式
定位观点定位某个观点在文献中的蛛丝马迹
加入知识库完成数据提取，报告撰写等更多高级知识挖掘功能

主要研究问题 ​

  1. 在使用neoCOR模型时，如何选择合适的肿瘤相关突变组合以获得不同类型的脑肿瘤？
  2. neoCOR模型在药物评估中的具体应用案例有哪些，特别是在针对特定DNA异常的情况下？
  3. 目前在脑肿瘤研究中，neoCOR模型与其他三维培养模型相比，有哪些独特的优势和局限性？
  4. 在临床转化研究中，neoCOR模型如何帮助识别新的治疗靶点或生物标志物？
  5. 对于不同类型的脑肿瘤，neoCOR模型的建立和研究方法是否需要调整，具体应如何进行优化？

核心洞察 ​

研究背景和目的 ​

脑肿瘤是最致命和破坏性最大的癌症之一，其研究受到遗传异质性和现有实验室模型不完整性的限制。为了解决这些问题，本研究的目的是建立一种三维体外模型——新生脑类器官（neoCOR），以重现脑肿瘤发生过程，并为脑肿瘤生物学的研究提供新的实验平台。

主要方法/材料/实验设计 ​

本研究采用转座子和CRISPR-Cas9介导的突变技术，在脑类器官中引入致癌突变。通过筛选在癌症基因组项目中识别的临床相关突变，确定了导致类胶质母细胞瘤和中枢神经系统原始神经外胚层肿瘤（CNS-PNET）样肿瘤的突变组合。

以下是研究的技术路线图：

Mermaid diagram

关键结果和发现 ​

  • 成功建立了新生脑类器官（neoCOR），可以重现脑肿瘤的发生。
  • 确定了特定的突变组合，这些组合能够导致类胶质母细胞瘤和CNS-PNET样肿瘤的形成。
  • neoCOR模型能够用于研究肿瘤的侵袭性以及特定DNA异常背景下药物的效果。

主要结论/意义/创新性 ​

本研究表明，neoCOR作为一种新型的三维模型，能够有效模拟脑肿瘤的生物学特性，提供了对肿瘤生物学的深入理解和药物筛选的新平台。其创新性在于结合了转座子和CRISPR-Cas9技术，为研究脑肿瘤的复杂性提供了新的工具和视角。

研究局限性和未来方向 ​

  • 研究中可能存在模型的局限性，如与真实肿瘤微环境的差异。
  • 未来研究可以扩展到不同类型的脑肿瘤，探索neoCOR在个性化医疗和新药开发中的应用潜力。
  • 建议结合临床数据进一步验证模型的有效性和可靠性。

参考文献 ​

  1. Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells. - Jichang Wang;Gangcai Xie;Manvendra Singh;Avazeh T Ghanbarian;Tamás Raskó;Attila Szvetnik;Huiqiang Cai;Daniel Besser;Alessandro Prigione;Nina V Fuchs;Gerald G Schumann;Wei Chen;Matthew C Lorincz;Zoltán Ivics;Laurence D Hurst;Zsuzsanna Izsvák - Nature (2014)
  2. An Organoid-Based Model of Cortical Development Identifies Non-Cell-Autonomous Defects in Wnt Signaling Contributing to Miller-Dieker Syndrome. - Vira Iefremova;George Manikakis;Olivia Krefft;Ammar Jabali;Kevin Weynans;Ruven Wilkens;Fabio Marsoner;Björn Brändl;Franz-Josef Müller;Philipp Koch;Julia Ladewig - Cell reports (2017)
  3. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. - David N Louis;Arie Perry;Guido Reifenberger;Andreas von Deimling;Dominique Figarella-Branger;Webster K Cavenee;Hiroko Ohgaki;Otmar D Wiestler;Paul Kleihues;David W Ellison - Acta neuropathologica (2016)
  4. Expression of estrogen and progesterone receptors in astrocytomas: a literature review. - Cléciton Braga Tavares;Francisca das Chagas Sheyla Almeida Gomes-Braga;Danylo Rafhael Costa-Silva;Carla Solange Escórcio-Dourado;Umbelina Soares Borges;Airton Mendes Conde-Junior;Maria da Conceição Barros-Oliveira;Emerson Brandão Sousa;Lorena da Rocha Barros;Luana Mota Martins;Gil Facina;Benedito Borges da-Silva - Clinics (Sao Paulo, Brazil) (2016)
  5. Pten haploinsufficiency accelerates formation of high-grade astrocytomas. - Chang-Hyuk Kwon;Dawen Zhao;Jian Chen;Sheila Alcantara;Yanjiao Li;Dennis K Burns;Ralph P Mason;Eva Y-H P Lee;Hong Wu;Luis F Parada - Cancer research (2008)
  6. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. - Yuan Zhu;Frantz Guignard;Dawen Zhao;Li Liu;Dennis K Burns;Ralph P Mason;Albee Messing;Luis F Parada - Cancer cell (2005)
  7. Differential expression of HIF-1 in glioblastoma multiforme and anaplastic astrocytoma. - Arnulf Mayer;Fabienne Schneider;Peter Vaupel;Clemens Sommer;Heinz Schmidberger - International journal of oncology (2012)
  8. Genome engineering using the CRISPR-Cas9 system. - F Ann Ran;Patrick D Hsu;Jason Wright;Vineeta Agarwala;David A Scott;Feng Zhang - Nature protocols (2013)
  9. An Ectopic Network of Transcription Factors Regulated by Hippo Signaling Drives Growth and Invasion of a Malignant Tumor Model. - Mardelle Atkins;Delphine Potier;Lucia Romanelli;Jelle Jacobs;Jana Mach;Fisun Hamaratoglu;Stein Aerts;Georg Halder - Current biology : CB (2016)
  10. Epithelial-mesenchymal transition in glioblastoma progression. - Yasuo Iwadate - Oncology letters (2016)

引用本文的文献 ​

  1. From Neuronal Differentiation of iPSCs to 3D Neuro-Organoids: Modelling and Therapy of Neurodegenerative Diseases. - Matteo Bordoni;Federica Rey;Valentina Fantini;Orietta Pansarasa;Anna Maria Di Giulio;Stephana Carelli;Cristina Cereda - International journal of molecular sciences (2018)
  2. Constructing and Deconstructing Cancers using Human Pluripotent Stem Cells and Organoids. - Ryan C Smith;Viviane Tabar - Cell stem cell (2019)
  3. Assessment of somatic single-nucleotide variation in brain tissue of cases with schizophrenia. - John F Fullard;Alexander W Charney;Georgios Voloudakis;Andrew V Uzilov;Vahram Haroutunian;Panos Roussos - Translational psychiatry (2019)
  4. 3D Bioprinted In Vitro Metastatic Models via Reconstruction of Tumor Microenvironments. - Fanben Meng;Carolyn M Meyer;Daeha Joung;Daniel A Vallera;Michael C McAlpine;Angela Panoskaltsis-Mortari - Advanced materials (Deerfield Beach, Fla.) (2019)
  5. Induced pluripotent stem cells in disease modelling and drug discovery. - R Grant Rowe;George Q Daley - Nature reviews. Genetics (2019)
  6. Using miniature brain implants in rodents for novel drug discovery. - Ben Waldau - Expert opinion on drug discovery (2019)
  7. The Use of Pluripotent Stem Cell-Derived Organoids to Study Extracellular Matrix Development during Neural Degeneration. - Yuanwei Yan;Julie Bejoy;Mark Marzano;Yan Li - Cells (2019)
  8. Brain organoids: advances, applications and challenges. - Xuyu Qian;Hongjun Song;Guo-Li Ming - Development (Cambridge, England) (2019)
  9. Bioengineering an Artificial Human Blood⁻Brain Barrier in Rodents. - Kimia Kamal;Ben Waldau - Bioengineering (Basel, Switzerland) (2019)
  10. Glioblastoma stem cells: lessons from the tumor hierarchy in a lethal cancer. - Ryan C Gimple;Shruti Bhargava;Deobrat Dixit;Jeremy N Rich - Genes & development (2019)

... (202 更多 篇文献)

© 2025 MaltSci 麦伴科研 - 我们用人工智能技术重塑科研