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Articles by Gaudenz Danuser
Thrombopoietin signaling and a dedicated cytoskeleton regulate murine hematopoietic stem cell motility
Abstract During development, transplantation, and homeostasis, hematopoietic stem cells (HSCs) migrate to niches to (re)constitute and maintain the hematopoietic system. A solid mechanistic understanding of their movement is essential but remains poorly examined. Here, we used long-term single-cell imaging and tracking to quantify how motility changes as immature HSCs differentiate into multipotent progenitors (MPPs), establishing motility as an early indicator of differentiation.
Highly multiplexed 3D profiling of cell states and immune niches in human tumors - Nature Methods
Abstract Diseases such as cancer involve alterations in cell proportions, states and interactions, as well as complex changes in tissue morphology and architecture. Histopathological diagnosis of disease and most multiplexed spatial profiling relies on inspecting thin (4–5 µm) specimens.
Imaging of cellular dynamics from a whole organism to subcellular scale with self-driving, multiscale microscopy - Nature Methods
Abstract Most biological processes, from development to pathogenesis, span multiple time and length scales. While light-sheet fluorescence microscopy has become a fast and efficient method for imaging organisms, cells and subcellular dynamics, simultaneous observations across all these scales have remained challenging.
Combinatorial responsiveness of single chemosensory neurons to external stimulation of mouse explants revealed by DynamicNeuronTracker
Abstract Calcium fluorescence imaging enables us to investigate how individual neurons of live animals encode sensory input or drive specific behaviors. Extracting and interpreting large-scale neuronal activity from imaging data are crucial steps in harnessing this information. A significant challenge arises from uncorrectable tissue deformation, which disrupts the effectiveness of existing neuron segmentation methods.
Compression-dependent microtubule reinforcement enables cells to navigate confined environments - Nature Cell Biology
Abstract Cells migrating through complex three-dimensional environments experience considerable physical challenges, including tensile stress and compression. To move, cells need to resist these forces while also squeezing the large nucleus through confined spaces. This requires highly coordinated cortical contractility. Microtubules can both resist compressive forces and sequester key actomyosin regulators to ensure appropriate activation of contractile forces.
Spatial proteomics of ER tubules reveals CLMN, an ER-actin tether at focal adhesions that promotes cell migration
Abstract The endoplasmic reticulum (ER) is structurally and functionally diverse, yet how its functions are organized within morphological subdomains is incompletely understood. Utilizing TurboID-based proximity labeling and CRISPR knock-in technologies, here we map the proteomic landscape of the human ER and nuclear envelope. Spatial proteomics reveals enrichments of proteins into ER tubules, sheets, and nuclear envelope.
Cellular harmonics for the morphology-invariant analysis of molecular organization at the cell surface - Nature Computational Science
Abstract The spatiotemporal organization of membrane-associated molecules is central to the regulation of cellular signals. Powerful new microscopy techniques enable the three-dimensional visualization of localization and activation of these molecules; however, the quantitative interpretation and comparison of molecular organization on the three-dimensional cell surface remains challenging because cells themselves vary greatly in morphology.
Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes
Loading metrics Open Access Peer-reviewed Research Article ? This is an uncorrected proof. Abstract We present an application of nonlinear image registration to align in microscopy time lapse sequences for every frame the cell outline and interior with the outline and interior of the same cell in a reference frame.
Remeshing flexible membranes under the control of free energy
Mechanical decoupling via deceleration of tension propagation Membrane tension is generally assumed to equilibrate across the entire cell almost instantaneously via diffusion of lipids [40]. However, a recent experiment [26] shows that this assumption is only valid for naive membranes, such as those in artificial giant unilamellar vesicles (GUV) [41] or blebby regions of HeLa cells [26], but not for complex membranes near the cytoskeleton.
Cellular Harmonics for the Morphology-invariant Analysis of Molecular Organization at the Cell Surface
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Fine-grained, nonlinear image registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes
Fine-grained, nonlinear image registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes Xuexia Jiang, Tadamoto Isogai, Joseph Chi, Gaudenz Danuser bioRxiv 2021.11.22.469497; doi: https://doi.org/10.1101/2021.11.22.469497
SH3BP4 promotes neuropilin-1 and α5-integrin endocytosis and is inhibited by Akt
Highlights • SH3BP4 promotes neuropilin-1 and α5-integrin endocytosis and semaphorin-3a signaling • Semaphorin-3a activates SH3BP4 via PTEN to promote cell contraction by endocytosis • AKT phosphorylates SH3BP4 at S246, excluding SH3BP4 from clathrin-coated pits • 14-3-3 binding to S246 blocks SH3BP4 complex with Eps15, GIPC1 to curb endocytosis Summary Cells probe their surrounding matrix for attachment sites via integrins that are internalized by endocytosis.
Estimation of the fraction of COVID-19 infected people in U.S. states and countries worldwide
Loading metrics Open Access Peer-reviewed Research Article Jungsik Noh , Gaudenz Danuser Jungsik Noh, Gaudenz Danuser Published: February 8, 2021 https://doi.org/10.1371/journal.pone.0246772 Figures Abstract Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, daily counts of confirmed cases and deaths have been publicly reported in real-time to control the virus spread.
An image-based assay to quantify changes in proliferation and viability upon drug treatment in 3D microenvironments
BMC Cancer201919:502 https://doi.org/10.1186/s12885-019-5694-1 © The Author(s). 2019 Received: 12 July 2018 Accepted: 8 May 2019 Published: 28 May 2019 Abstract Background Every biological experiment requires a choice of throughput balanced against physiological relevance. Most primary drug screens neglect critical parameters such as microenvironmental conditions, cell-cell heterogeneity, and specific readouts of cell fate for the sake of throughput.
Quantitative Multiscale Cell Imaging in Controlled 3D Microenvironments
A Microscope Designed for Multiscale Isotropic Imaging of Subcellular Biology in 3D Effects of 2D and 3D Microenvironments on Cell Morphology Multiscale Imaging Enables Simultaneous Observation of Subcellular Features and the Microenvironment Control over the Microenvironment Enables Observation of Spontaneous and Ubiquitous Pressure-Based Protrusions 3D Isotropic Resolution Enables Quantification of Protein Localization and Activity in Live Cells Blebs are characterized by uniform or regular...
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