Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms

Liu, Tsung‐Li; Upadhyayula, Srigokul; Milkie, Daniel E.; Singh, Ved; Wang, Kai; Swinburne, Ian A.; Mosaliganti, Kishore; Collins, Zachary; Hiscock, Tom W.; Shea, Jamien; Kohrman, Abraham; Medwig, Taylor N; Dambournet, Daphné; Forster, Ryan; Cunniff, Brian; Ruan, Yuan; Yashiro, Hanako; Scholpp, Steffen; Meyerowitz, Elliot M.; Hockemeyer, Dirk; Drubin, David G.; Martin, Benjamin L.; Matus, David Q.; Koyama, Minoru; Megason, Sean G.; Kirchhausen, Tom; Betzig, Eric

doi:10.1126/science.aaq1392

Cited by 499 publications

(394 citation statements)

References 74 publications

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“…There is no doubt that advances in intravital imaging have revolutionized the analysis of biological systems [33,34]. Intravital imaging using multiphoton microscopy is a powerful technique capable of directly visualizing the phenotypes of individual cancer, immune, and other stromal cells, and their interactions in both intact solid tumors and in target organs.…”

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

The Different Routes to Metastasis via Hypoxia-Regulated Programs

Nobre

Entenberg

Wang

et al. 2018

Trends in Cell Biology

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Hypoxia is linked to metastasis; however, how it affects metastatic progression is not clear due to limited consensus in the literature. We posit that this lack of consensus is due to hypoxia being studied using different approaches, such as in vitro, primary tumor, or metastasis assays in an isolated manner. Here, we review the pros and cons of in vitro hypoxia assays, highlight in vivo studies that inform on physiological hypoxia, and review the evidence that primary tumor hypoxia might influence the fate of disseminated tumor cells (DTCs) in secondary organs. Our analysis suggests that consensus can be reached by using in vivo methods of study, which also allow better modeling of how hypoxia affects DTC fate and metastasis.

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Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

The Different Routes to Metastasis via Hypoxia-Regulated Programs

Nobre

Entenberg

Wang

et al. 2018

Trends in Cell Biology

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“…Multiple aspects of myelin development have been discovered using zebrafish as discussed below. Advances in superresolution (Liu et al, ) and high frame‐rate microscopy techniques (Ahrens & Engert, ) combined with the development of genetically encoded sensors for calcium, membrane voltage, and other intracellular ions and neurotransmitters are all likely to provide axonal functional readouts associated with changes in myelination in the coming years.…”

Section: Optical Approaches For Live Myelin Imagingmentioning

confidence: 99%

Uncovering the biology of myelin with optical imaging of the live brain

Hill

Grutzendler

2019

Glia

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Myelin has traditionally been considered a static structure that is produced and assembled during early developmental stages. While this characterization is accurate in some contexts, recent studies have revealed that oligodendrocyte generation and patterns of myelination are dynamic and potentially modifiable throughout life. Unique structural and biochemical properties of the myelin sheath provide opportunities for the development and implementation of multimodal label‐free and fluorescence optical imaging approaches. When combined with genetically encoded fluorescent tags targeted to distinct cells and subcellular structures, these techniques offer a powerful methodological toolbox for uncovering mechanisms of myelin generation and plasticity in the live brain. Here, we discuss recent advances in these approaches that have allowed the discovery of several forms of myelin plasticity in developing and adult nervous systems. Using these techniques, long‐standing questions related to myelin generation, remodeling, and degeneration can now be addressed.

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“…These model systems are highly informative for studying evolutionary conserved mechanisms, despite limitations in their multicellular complexity and tissue functionality. Another aspect to consider is that light sheet microscopy, just as any other fluorescence imaging techniques, suffers from effects of scattering and absorption, which poses technical challenges in deep tissue imaging .…”

Section: Scale‐crossing Technologiesmentioning

confidence: 99%

From single cells to tissue self‐organization

Santos

Liberali

2018

The FEBS Journal

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Self‐organization is a process by which interacting cells organize and arrange themselves in higher order structures and patterns. To achieve this, cells must have molecular mechanisms to sense their complex local environment and interpret it to respond accordingly. A combination of cell‐intrinsic and cell‐extrinsic cues are decoded by the single cells dictating their behaviour, their differentiation and symmetry‐breaking potential driving development, tissue remodeling and regenerative processes. A unifying property of these self‐organized pattern‐forming systems is the importance of fluctuations, cell‐to‐cell variability, or noise. Cell‐to‐cell variability is an inherent and emergent property of populations of cells that maximize the population performance instead of the individual cell, providing tissues the flexibility to develop and maintain homeostasis in diverse environments. In this review, we will explore the role of self‐organization and cell‐to‐cell variability as fundamental properties of multicellularity—and the requisite of single‐cell resolution for its understanding. Moreover, we will analyze how single cells generate emergent multicellular dynamics observed at the tissue level ‘travelling’ across different scales: spatial, temporal and functional.

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Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms

Cited by 499 publications

References 74 publications

The Different Routes to Metastasis via Hypoxia-Regulated Programs

The Different Routes to Metastasis via Hypoxia-Regulated Programs

Uncovering the biology of myelin with optical imaging of the live brain

From single cells to tissue self‐organization

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