scholarly journals Heterogeneous T cell motility behaviors emerge from a coupling between speed and turning in vivo

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Elizabeth R Jerison ◽  
Stephen R Quake
Keyword(s):  
T Cells ◽  
Random Walks ◽  
Light Sheet ◽  
Model System ◽  
Light Sheet Microscopy ◽  
Larval Zebrafish ◽  
Large Populations ◽  
Native Context ◽  
Cell To Cell Variability

T cells in vivo migrate primarily via undirected random walks, but it remains unresolved how these random walks generate an efficient search. Here, we use light sheet microscopy of T cells in the larval zebrafish as a model system to study motility across large populations of cells over hours in their native context. We show that cells do not perform Levy flight; rather, there is substantial cell-to-cell variability in speed, which persists over timespans of a few hours. This variability is amplified by a correlation between speed and directional persistence, generating a characteristic cell behavioral manifold that is preserved under a perturbation to cell speeds, and seen in Mouse T cells and Dictyostelium. Together, these effects generate a broad range of length scales over which cells explore in vivo.

scholarly journals Heterogeneous T cell motility behaviors emerge from a coupling between speed and turning in vivo

2019 ◽  
Author(s):  
Elizabeth R. Jerison ◽  
Stephen R. Quake
Keyword(s):  
T Cells ◽  
Random Walks ◽  
Cell Motility ◽  
Light Sheet ◽  
Light Sheet Microscopy ◽  
Larval Zebrafish ◽  
Large Populations ◽  
Cell To Cell Variability ◽  
Ameboid Cell

AbstractT cells in vivo migrate primarily via undirected random walks, but it remains unresolved how these random walks generate an efficient search. Here, we use light sheet microscopy of T cells in the larval zebrafish as a model system to study motility across large populations of cells over hours in their native context. We show that cell-to-cell variability is amplified by a correlation between speed and directional persistence, generating a characteristic cell behavioral manifold that is preserved under a perturbation to cell speeds, and seen in Mouse T cells and Dictyostelium. These results suggest that there is a single variable underlying ameboid cell motility that jointly controls speed and turning. This coupling explains behavioral heterogeneity in diverse systems and allows cells to access a broad range of length scales.

scholarly journals Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells in cancer

2021 ◽  
Author(s):  
Kelly Kersten ◽  
Kenneth H Hu ◽  
Alexis J Combes ◽  
Bushra Samad ◽  
Tory Harwin ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Light Sheet ◽  
Light Sheet Microscopy ◽  
Spatially Resolved ◽  
Hypoxic Conditions ◽  
Synaptic Interactions ◽  
Positive Feedback Circuit ◽  
Major Impediment

T cell exhaustion is a major impediment to anti-tumor immunity. However, it remains elusive how other immune cells in the tumor microenvironment (TME) contribute to this dysfunctional state. Here we show that the biology of tumor-associated macrophages (TAM) and exhausted T cells (Tex) in the TME is extensively linked. We demonstrate that in vivo depletion of TAM reduces exhaustion programs in tumor-infiltrating CD8+ T cells and reinvigorates their effector potential. Reciprocally, transcriptional and epigenetic profiling reveals that Tex express factors that actively recruit monocytes to the TME and shape their differentiation. Using lattice light sheet microscopy, we show that TAM and CD8+ T cells engage in unique long-lasting antigen-specific synaptic interactions that fail to activate T cells, but prime them for exhaustion, which is then accelerated in hypoxic conditions. Spatially resolved sequencing supports a spatiotemporal self-enforcing positive feedback circuit that is aligned to protect rather than destroy a tumor.

Multiphoton Light-sheet Microscopy at Optimal Pulse Frequency for Fast In Vivo Imaging

2020 ◽  
Author(s):  
Vincent Maioli ◽  
Antoine Boniface ◽  
Pierre Mahou ◽  
Júlia Ferrer Ortas ◽  
Lamiae Abdeladim ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Light Sheet ◽  
Pulse Frequency ◽  
Light Sheet Microscopy

scholarly journals Coupling optogenetics and light-sheet microscopy to study signal transduction in vivo

2017 ◽  
Vol 145 ◽  
pp. S70-S71
Author(s):  
Prameet Kaur ◽  
Timothy E. Saunders ◽  
Nicholas Tolwinski
Keyword(s):  
Signal Transduction ◽  
Light Sheet ◽  
Light Sheet Microscopy

Functional in vivo imaging using fluorescence lifetime light sheet microscopy (Conference Presentation)

2019 ◽  
Author(s):  
Simon M. Ameer-Beg ◽  
Claire A. Mitchell ◽  
Simon P. Poland ◽  
Robert D. Knight ◽  
Guoqing Wang ◽  
...  
Keyword(s):  
Fluorescence Lifetime ◽  
In Vivo Imaging ◽  
Light Sheet ◽  
Light Sheet Microscopy

In vivo light‐sheet microscopy resolves localisation patterns of FSD1 , a superoxide dismutase with function in root development and osmoprotection

2020 ◽  
Vol 44 (1) ◽  
pp. 68-87 ◽  
Author(s):  
Petr Dvořák ◽  
Yuliya Krasylenko ◽  
Miroslav Ovečka ◽  
Jasim Basheer ◽  
Veronika Zapletalová ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Root Development ◽  
Light Sheet ◽  
Light Sheet Microscopy

scholarly journals Whole-brain calcium imaging during physiological vestibular stimulation in larval zebrafish

2018 ◽  
Author(s):  
Geoffrey Migault ◽  
Thomas Panier ◽  
Raphaël Candelier ◽  
Georges Debrégeas ◽  
Volker Bormuth
Keyword(s):  
Virtual Environments ◽  
Functional Imaging ◽  
Light Sheet ◽  
Vestibular Stimulation ◽  
Brain Response ◽  
Whole Brain ◽  
Larval Zebrafish ◽  
In Vivo Functional Imaging ◽  
First Time

AbstractDuring in vivo functional imaging, animals are head-fixed and thus deprived from vestibular inputs, which severely hampers the design of naturalistic virtual environments. To overcome this limitation, we developed a miniaturized ultra-stable light-sheet microscope that can be dynamically rotated during imaging along with a head-restrained zebrafish larva. We demonstrate that this system enables whole-brain functional imaging at single-cell resolution under controlled vestibular stimulation. We recorded for the first time the dynamic whole-brain response of a vertebrate to physiological vestibular stimulation. This development largely expands the potential of virtual-reality systems to explore complex multisensory-motor integration in 3D.

scholarly journals Observing the Cell in Its Native State: Imaging Subcellular Dynamics in Multicellular Organisms

2018 ◽  
Author(s):  
Tsung-Li Liu ◽  
Srigokul Upadhyayula ◽  
Daniel E. Milkie ◽  
Ved Singh ◽  
Kai Wang ◽  
...  
Keyword(s):  
Adaptive Optics ◽  
High Speed ◽  
Developmental Stages ◽  
Phenotypic Diversity ◽  
Metastatic Cancer ◽  
Light Sheet ◽  
Intrinsic Variability ◽  
Spatiotemporal Resolution ◽  
Light Sheet Microscopy

AbstractTrue physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution without inducing undue stress on either. We combined lattice light sheet microscopy with two-channel adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages, and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.One Sentence SummaryCombining lattice light sheet microscopy with adaptive optics enables high speed, high resolution in vivo 3D imaging of dynamic processes inside cells under physiological conditions within their parent organisms.

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