Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging.
Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging.
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生物分子的亚细胞定位和药物分布的高清晰度离子束成像。
DOI：
10.1038/s41467-021-24822-1
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发表时间：
2021-07-30
影响因子：
16.6
通讯作者：
Nolan GP
中科院分区：
文献类型：
--
作者：
Rovira-Clavé X;Jiang S;Bai Y;Zhu B;Barlow G;Bhate S;Coskun AF;Han G;Ho CK;Hitzman C;Chen SY;Bava FA;Nolan GP
同时可视化多个生物分子及其配体或细胞内纳米尺度的小分子之间的关系，将有助于更好地理解生物过程是如何运作的。我们在这里提出了高清多路离子束成像（HD-MIBI），这是一种二次离子质谱方法，能够对目标生物实体和外源添加的结构未修饰的小分子进行高参数三维成像。有了这项技术，生物分子本身的原子成分可以在我们的系统中用作“标签”，我们展示了测量到~30纳米的横向分辨率。我们将化疗药物顺铂的亚细胞定位与五个亚核结构同时联系起来。顺铂优先富集于核斑点，排除在封闭染色质区域，表明顺铂在染色质活性区域的作用。出乎意料的是，在顺铂和BET抑制剂JQ1的多药治疗中存活的细胞几乎完全从细胞核中排除了顺铂，这表明选择性亚细胞药物重新定位可能调节了对这种重要化疗治疗的耐药性。多路高分辨率成像技术，如HD-MIBI，将使生物分子和药物分布在生物相关的亚细胞微环境中的研究成为可能，方法是将过程本身可视化，而不是通过替代分析来推断机制。多路离子束成像可以提供亚细胞定位信息，但分辨率有限。在这里，作者报告了一种纳米级分辨率的离子束成像方法，他们用它来评估顺铂的亚细胞分布。
Simultaneous visualization of the relationship between multiple biomolecules and their ligands or small molecules at the nanometer scale in cells will enable greater understanding of how biological processes operate. We present here high-definition multiplex ion beam imaging (HD-MIBI), a secondary ion mass spectrometry approach capable of high-parameter imaging in 3D of targeted biological entities and exogenously added structurally-unmodified small molecules. With this technology, the atomic constituents of the biomolecules themselves can be used in our system as the “tag” and we demonstrate measurements down to ~30 nm lateral resolution. We correlated the subcellular localization of the chemotherapy drug cisplatin simultaneously with five subnuclear structures. Cisplatin was preferentially enriched in nuclear speckles and excluded from closed-chromatin regions, indicative of a role for cisplatin in active regions of chromatin. Unexpectedly, cells surviving multi-drug treatment with cisplatin and the BET inhibitor JQ1 demonstrated near total cisplatin exclusion from the nucleus, suggesting that selective subcellular drug relocalization may modulate resistance to this important chemotherapeutic treatment. Multiplexed high-resolution imaging techniques, such as HD-MIBI, will enable studies of biomolecules and drug distributions in biologically relevant subcellular microenvironments by visualizing the processes themselves in concert, rather than inferring mechanism through surrogate analyses. Multiplexed ion beam imaging can provide subcellular localisation information but with limited resolution. Here the authors report an ion beam imaging method with nanoscale resolution which they use to assess the subcellular distribution of cisplatin.
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影响因子：
64.5
作者：
Cleary B;Cong L;Cheung A;Lander ES;Regev A
通讯作者：
Regev A
光学成像。膨胀显微镜。
DOI：
10.1126/science.1260088
发表时间：
2015-01-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen F;Tillberg PW;Boyden ES
通讯作者：
Boyden ES
影响因子：
64.5
作者：
Goltsev Y;Samusik N;Kennedy-Darling J;Bhate S;Hale M;Vazquez G;Black S;Nolan GP
通讯作者：
Nolan GP
选择性抑制BET溴结构域。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Guo, Syuan-Ming;Veneziano, Remi;Bathe, Mark
通讯作者：
Bathe, Mark