Ultrastructural visualization of chromatin in cancer pathogenesis using a simple small-molecule fluorescent probe

使用简单的小分子荧光探针对癌症发病机制中的染色质进行超微结构可视化

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作者:Jianquan Xu, Xuejiao Sun, Kwangho Kim, Rhonda M Brand, Douglas Hartman, Hongqiang Ma, Randall E Brand, Mingfeng Bai, Yang Liu

Abstract

Imaging chromatin organization at the molecular-scale resolution remains an important endeavor in basic and translational research. Stochastic optical reconstruction microscopy (STORM) is a powerful superresolution imaging technique to visualize nanoscale molecular organization down to the resolution of ~20 to 30 nm. Despite the substantial progress in imaging chromatin organization in cells and model systems, its routine application on assessing pathological tissue remains limited. It is, in part, hampered by the lack of simple labels that consistently generates high-quality STORM images on the highly processed clinical tissue. We developed a fast, simple, and robust small-molecule fluorescent probe-cyanine 5-conjugated Hoechst-for routine superresolution imaging of nanoscale nuclear architecture on clinical tissue. We demonstrated the biological and clinical significance of imaging superresolved chromatin structure in cancer development and its potential clinical utility for cancer risk stratification.

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