2020
DOI: 10.1038/s41467-020-15718-7
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Super-resolution imaging reveals the evolution of higher-order chromatin folding in early carcinogenesis

Abstract: Genomic DNA is folded into a higher-order structure that regulates transcription and maintains genomic stability. Although progress has been made on understanding biochemical characteristics of epigenetic modifications in cancer, the in-situ higher-order folding of chromatin structure during malignant transformation remains largely unknown. Here, using optimized stochastic optical reconstruction microscopy (STORM) for pathological tissue (PathSTORM), we uncover a gradual decompaction and fragmentation of highe… Show more

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Cited by 73 publications
(85 citation statements)
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“…Therefore, we speculate that our observation of the stem-like intermediate state during cancer formation may likely be observed by the other types of cancer. Recent experimental observations that the chromosome opening its structure in the early stages of tumor formation is regardless of cancer types and shares a similar trait of chromosome organization with the stem cell provide evidence of our theoretical findings and speculations our speculation [108,109]. The open chromosome structure in the stem-like intermediate state may contribute to the increased genomic instability and active transcription for cells to gain plasticity that has been demonstrated as the universal key to facilitate cancer progression [110].…”
Section: Discussion and Conclu-sionssupporting
confidence: 63%
“…Therefore, we speculate that our observation of the stem-like intermediate state during cancer formation may likely be observed by the other types of cancer. Recent experimental observations that the chromosome opening its structure in the early stages of tumor formation is regardless of cancer types and shares a similar trait of chromosome organization with the stem cell provide evidence of our theoretical findings and speculations our speculation [108,109]. The open chromosome structure in the stem-like intermediate state may contribute to the increased genomic instability and active transcription for cells to gain plasticity that has been demonstrated as the universal key to facilitate cancer progression [110].…”
Section: Discussion and Conclu-sionssupporting
confidence: 63%
“…Excited at the potential to visualize in situ pathological tissues in a clinical setting, we visualized the initiation and stepwise progression of murine precancerous and cancerous heterochromatin to compare to that from normal, non-anomalous tissues. 6 What we found was a decompaction of mouse heterochromatin over the course of tumorigenesis before morphological changes to cells visible using conventional microscopy. This decompaction was a gradual process, not one sparked by a singular event and completed quickly.…”
mentioning
confidence: 75%
“…Enter PathSTORM – a super-resolution technique optimized for the robust, reproducible, and high-quality imaging of heterogeneous pathological tissues ( Figure 1a ). 6 This technique incorporated three major advances in STORM imaging: reduction in background signal through optical clearing and buffer optimization, an enhanced background correction algorithm, and a high-speed, high-fidelity image reconstruction algorithm. With these optimizations, reproducible high-quality super-resolution imaging of pathological samples suddenly became possible.…”
mentioning
confidence: 99%
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“…Here we present a detailed protocol for PathSTORM, a variant of STORM that combines optimized sample preparation and high-fidelity image reconstruction for high-quality super-resolution imaging of densely packed higher-order chromatin organization in pathological tissue. We have recently demonstrated the ability of PathSTORM to detect disrupted chromatin folding at the nanoscale level, which may potentially be used to detect early-stage carcinogenesis in clinical tissue samples (Xu et al, 2020).…”
Section: Introductionmentioning
confidence: 99%