Super-resolution fluorescence-assisted diffraction computational tomography reveals the three-dimensional landscape of the cellular organelle interactome

Dong, Dashan; Huang, Xiaoshuai; Li, Liuju; Mao, Heng; Mo, Yanquan; Zhang, Guangyi; Zhang, Zhe; Shen, Jiayu; Liu, Wei; Wu, Zeming; Liu, Guanghui; Liu, Yanmei; Yang, Hong; Gong, Qihuang; Shi, Kebin; Chen, Liangyi

doi:10.1038/s41377-020-0249-4

Cited by 85 publications

(46 citation statements)

References 53 publications

(73 reference statements)

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“…To test this hypothesis, we employed the selective ACAT inhibitor, Sandoz 58-035 (SZ58-035), to determine the role of ACAT in modulating accessible cholesterol and suppressing SARS-CoV-2 pseudovirus entry (Fig 4A). Since upon esterification by ACAT, cholesteryl esters are stored in cytosolic lipid droplets, we used a lipid droplet stain to monitor ACAT activity (Dong et al, 2020). We first confirmed that 25HC could activate ACAT by staining intracellular lipid droplets in vehicle-or 25HC-treated Calu-3 cells.…”

Section: -Hydroxycholesterol (25hc) Broadly Inhibits Viral Entry Ofmentioning

confidence: 75%

Cholesterol 25‐Hydroxylase inhibits SARS ‐CoV‐2 and other coronaviruses by depleting membrane cholesterol

et al. 2020

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Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and has spread across the globe. SARS-CoV-2 is a highly infectious virus with no vaccine or antiviral therapy available to control the pandemic; therefore, it is crucial to understand the mechanisms of viral pathogenesis and the host immune responses to SARS-CoV-2. SARS-CoV-2 is a new member of the betacoronavirus genus like other closely related viruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Both SARS-CoV and MERS-CoV have caused serious outbreaks and epidemics in the past eighteen years. Here, we report that one of the interferon-stimulated genes (ISGs), cholesterol 25-hydroxylase (CH25H), is induced by SARS-CoV-2 infection in vitro and in COVID-19-infected patients. CH25H converts cholesterol to 25-hydrocholesterol (25HC) and 25HC shows broad anti-coronavirus activity by blocking membrane fusion. Furthermore, 25HC inhibits USA-WA1/2020 SARS-CoV-2 infection in lung epithelial cells and viral entry in human lung organoids. Mechanistically, 25HC inhibits viral membrane fusion by activating the ER-localized acyl-CoA:cholesterol acyltransferase (ACAT) which leads to the depletion of accessible cholesterol from the plasma membrane. Altogether, our results shed light on a potentially broad antiviral mechanism by 25HC through depleting accessible cholesterol on the plasma membrane to suppress virus-cell fusion. Since 25HC is a natural product with no known toxicity at effective concentrations, it provides a potential therapeutic candidate for COVID-19 and emerging viral diseases in the future.

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Section: -Hydroxycholesterol (25hc) Broadly Inhibits Viral Entry Ofmentioning

confidence: 75%

Cholesterol 25‐Hydroxylase inhibits SARS ‐CoV‐2 and other coronaviruses by depleting membrane cholesterol

et al. 2020

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“…In addition, SIM based on Hessian matrixes excels in extending the spatiotemporal resolution in live cells and is expected to apply for studying MCSs in COS-7 cells (Huang et al, 2018). More importantly, super-resolution fluorescenceassisted diffraction computational tomography (SR-FACT) was developed by combination of label-free three-dimensional optical diffraction tomography (ODT) with two-dimensional fluorescence Hessian structured illumination microscopy (Dong et al, 2020). The SR-FACT enable label-free visualization of various subcellular structures and complete division process of a COS-7 cell.…”

Section: Visualization Of Mcss By Em and Srmmentioning

confidence: 99%

“…The SR-FACT enable label-free visualization of various subcellular structures and complete division process of a COS-7 cell. By using SR-FACT, novel subcellular structures named dark-vacuole bodies (DB) were observed, and intensively contact with organelles such as mitochondria and nuclear membrane in COS-7 cells (Dong et al, 2020).…”

Section: Visualization Of Mcss By Em and Srmmentioning

confidence: 99%

Current and Emerging Approaches for Studying Inter-Organelle Membrane Contact Sites

Huang

Jiang

et al. 2020

Front. Cell Dev. Biol.

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Inter-organelle membrane contact sites (MCSs) are classically defined as areas of close proximity between heterologous membranes and established by specific proteins (termed tethers). The interest on MCSs has rapidly increased in the last years, since MCSs play a crucial role in the transfer of cellular components between different organelles and have been involved in important cellular functions such as apoptosis, organelle division and biogenesis, and cell growth. Recently, an unprecedented depth and breadth in insights into the details of MCSs have been uncovered. On one hand, extensive MCSs (organelles interactome) are revealed by comprehensive analysis of organelle network with high temporal-spatial resolution at the system level. On the other hand, more and more tethers involving in MCSs are identified and further works are focusing on addressing the role of these tethers in regulating the function of MCSs at the molecular level. These enormous progresses largely depend on the powerful approaches, including several different types of microscopies and various biochemical techniques. These approaches have greatly accelerated recent advances in MCSs at the system and molecular level. In this review, we summarize the current and emerging approaches for studying MCSs, such as various microscopies, proximity-driven fluorescent signal generation and proximity-dependent biotinylation. In addition, we highlight the advantages and disadvantages of the techniques to provide a general guidance for the study of MCSs.

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“…The numbers of clusters were 2, 3 and 2. Gaussian noise with a mean value of 0 and a mean square error of 30%, 20% and 30% and salt-and-pepper noise were added to synthetic images 2 and 3, with 2 clusters each [53,54] The segmentation test results for the remote sensing images shown in Figures 16-20 indicate that the FCM and FFSCM algorithms have large numbers of noise points. The SVFMM algorithm considers the influence of the neighbourhood space, and it suppresses noise points.…”

Section: Image Segmentation Test With Mixed Noisementioning

confidence: 99%

An Adaptive Feature Selection Algorithm for Fuzzy Clustering Image Segmentation Based on Embedded Neighbourhood Information Constraints

Ren

2020

Sensors

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This paper addresses the lack of robustness of feature selection algorithms for fuzzy clustering segmentation with the Gaussian mixture model. Assuming that the neighbourhood pixels and the centre pixels obey the same distribution, a Markov method is introduced to construct the prior probability distribution and achieve the membership degree regularisation constraint for clustering sample points. Then, a noise smoothing factor is introduced to optimise the prior probability constraint. Second, a power index is constructed by combining the classification membership degree and prior probability since the Kullback–Leibler (KL) divergence of the noise smoothing factor is used to supervise the prior probability; this probability is embedded into Fuzzy Superpixels Fuzzy C-means (FSFCM) as a regular factor. This paper proposes a fuzzy clustering image segmentation algorithm based on an adaptive feature selection Gaussian mixture model with neighbourhood information constraints. To verify the segmentation performance and anti-noise robustness of the improved algorithm, the fuzzy C-means clustering algorithm Fuzzy C-means (FCM), FSFCM, Spatially Variant Finite Mixture Model (SVFMM), EGFMM, extended Gaussian mixture model (EGMM), adaptive feature selection robust fuzzy clustering segmentation algorithm (AFSFCM), fast and robust spatially constrained Gaussian mixture model (GMM) for image segmentation (FRSCGMM), and improve method are used to segment grey images containing Gaussian noise, salt-and-pepper noise, multiplicative noise and mixed noise. The peak signal-to-noise ratio (PSNR) and the error rate (MCR) are used as the theoretical basis for assessing the segmentation results. The improved algorithm indicators proposed in this paper are optimised. The improved algorithm yields increases of 0.1272–12.9803 dB, 1.5501–13.4396 dB, 1.9113–11.2613 dB and 1.0233–10.2804 dB over the other methods, and the Misclassification rate (MSR) decreases by 0.32–37.32%, 5.02–41.05%, 0.3–21.79% and 0.9–30.95% compared to that with the other algorithms. It is verified that the segmentation results of the improved algorithm have good regional consistency and strong anti-noise robustness, and they meet the needs of noisy image segmentation.

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Super-resolution fluorescence-assisted diffraction computational tomography reveals the three-dimensional landscape of the cellular organelle interactome

Cited by 85 publications

References 53 publications

Cholesterol 25‐Hydroxylase inhibits SARS ‐CoV‐2 and other coronaviruses by depleting membrane cholesterol

Cholesterol 25‐Hydroxylase inhibits SARS ‐CoV‐2 and other coronaviruses by depleting membrane cholesterol

Current and Emerging Approaches for Studying Inter-Organelle Membrane Contact Sites

An Adaptive Feature Selection Algorithm for Fuzzy Clustering Image Segmentation Based on Embedded Neighbourhood Information Constraints

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