Scott Fraser

Scott Fraser
University of Southern California | USC · Zilkha Neurogenetic Institute

PhD

About

576
Publications
59,098
Reads
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38,277
Citations
Citations since 2017
108 Research Items
10227 Citations
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201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500

Publications

Publications (576)
Preprint
Developmental studies have revealed the importance of the transcription factor Hand2 in cardiac development. Hand2 promotes cardiac progenitor differentiation and epithelial maturation, while repressing other tissue types. The mechanisms underlying the promotion of cardiac fates are far better understood than those underlying the repression of alte...
Article
Glucose stimulated insulin secretion is mediated by glucose metabolism via oxidative phosphorylation generating ATP that triggers membrane depolarization and exocytosis of insulin. In stressed beta cells, glucose metabolism is remodeled, with enhanced glycolysis uncoupled from oxidative phosphorylation, resulting in the impaired glucose-mediated in...
Article
Study question To classify embryos according to their metabolic fingerprint with a robust, non-invasive methodology Summary answer Our Hyperspectral (HS) phasor analysis coupled to artificial intelligence simultaneously detects 6+ metabolites to profile and classify competent embryos and oocytes safely and consistently. What is known already Meta...
Article
Full-text available
Styrene dyes are useful imaging probes and fluorescent sensors due to their strong fluorogenic responses to environmental changes or binding macromolecules. Previously, indole-containing styrene dyes have been reported to selectively bind RNA in the nucleolus and cytoplasm. However, the application of these indole-based dyes in cell imaging is limi...
Preprint
Full-text available
In functional imaging studies, accurately synchronizing the time course of experimental manipulations and stimulus presentations with resulting imaging data is crucial for analysis. Current software tools lack such functionality, requiring manual processing of the experimental and imaging data, which is error-prone and potentially non-reproducible....
Article
In functional imaging studies, accurately synchronizing the time course of experimental manipulations and stimulus presentations with resulting imaging data is crucial for analysis. Current software tools lack such functionality, requiring manual processing of the experimental and imaging data, which is error-prone and potentially non-reproducible....
Preprint
Full-text available
Fluorescent reporter pluripotent stem cell (PSC) derived retinal organoids are powerful tools to investigate cell type-specific development and disease phenotypes. When combined with live imaging, they enable direct and repeated observation of cell behaviors within a developing retinal tissue. Here, we generated a human cone photoreceptor reporter...
Article
Full-text available
Hyperspectral fluorescence imaging improves multiplexed observations of biological samples by utilizing multiple color channels across the spectral range to compensate for spectral overlap between labels. Typically, spectral resolution comes at a cost of decreased detection efficiency, which both hampers imaging speed and increases photo-toxicity t...
Article
Full-text available
The expansion of fluorescence bioimaging toward more complex systems and geometries requires analytical tools capable of spanning widely varying timescales and length scales, cleanly separating multiple fluorescent labels and distinguishing these labels from background autofluorescence. Here we meet these challenging objectives for multispectral fl...
Article
The breaking of bilateral symmetry in most vertebrates is critically dependent upon the motile cilia of the embryonic left-right organizer (LRO), which generate a directional fluid flow; however, it remains unclear how this flow is sensed. Here, we demonstrated that immotile LRO cilia are mechanosensors for shear force using a methodological pipeli...
Article
Full-text available
The sensitivity of the αβ T cell receptor (TCR) is enhanced by the coreceptors CD4 and CD8αβ, which are expressed primarily by cells of the helper and cytotoxic T cell lineages, respectively. The coreceptors bind to major histocompatibility complex (MHC) molecules and associate intracellularly with the Src-family kinase Lck, which catalyzes TCR pho...
Article
Full-text available
BAZ1B is an ubiquitously expressed nuclear protein with roles in chromatin remodelling, DNA replication and repair, and transcription. Reduced baz1b expression disrupts neuronal and neural crest development. Variation in the activity of baz1b has been proposed to underly morphological and behavioural aspects of domestication through disruption of n...
Article
Full-text available
Pancreatic β-cells respond to increased extracellular glucose levels by initiating a metabolic shift. That change in metabolism is part of the process of glucose-stimulated insulin secretion and is of particular interest in the context of diabetes. However, we do not fully understand how the coordinated changes in metabolic pathways and metabolite...
Article
Full-text available
Light-sheet microscopes must compromise among field of view, optical sectioning, resolution, and detection efficiency. High-numerical-aperture (NA) detection objective lenses provide higher resolution, but their narrow depth of field inefficiently captures the fluorescence signal generated throughout the thickness of the illumination light sheet wh...
Preprint
Full-text available
Precise control of cell division is essential for proper patterning and growth during the development of multicellular organisms. Coordination of formative (asymmetric) divisions that generate new tissue patterns with proliferative (symmetric) divisions that promote growth is poorly understood. Here, we employed quantitative 4D light sheet and conf...
Article
Visualizing cell shapes and interactions of differentiating cells is instrumental for understanding organ development and repair. Across species, strategies for stochastic multicolour labelling have greatly facilitated in vivo cell tracking and mapping neuronal connectivity. Yet integrating multi-fluorophore information into the context of developi...
Preprint
The sensitivity of the αβ T-cell receptor (TCR) is enhanced by the coreceptors CD4 and CD8αβ, which are expressed primarily by cells of the helper and cytotoxic T-cell lineages, respectively. The coreceptors bind to major histocompatibility complex (MHC) molecules and associate intracellularly with the Src-family kinase Lck, which catalyzes TCR pho...
Article
Full-text available
The broad sharing of research data is widely viewed as critical for the speed, quality, accessibility, and integrity of science. Despite increasing efforts to encourage data sharing, both the quality of shared data and the frequency of data reuse remain stubbornly low. We argue here that a significant reason for this unfortunate state of affairs is...
Article
Full-text available
Fluorescence lifetime imaging microscopy (FLIM) evaluates the metabolic state of tissue based on reduced nicotinamide adenine dinucleotide (NAD(P)H) and flavin adenine dinucleotide (FAD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) can image the fundus of the eyes, but cannot detect NAD(P)H. We used multiphoton FLIM to study the metabolic s...
Article
Full-text available
An ability to estimate quantities, such as the number of conspecifics or the size of a predator, has been reported in vertebrates. Fish, in particular zebrafish, may be instrumental in advancing the understanding of magnitude cognition. We review here the behavioral studies that have described the ecological relevance of quantity estimation in fish...
Preprint
Light-sheet microscopes must compromise between field of view, optical sectioning, resolution, and detection efficiency. High-numerical-aperture (NA) detection objective lenses provide high resolution but their narrow depth of field fails to capture effectively the fluorescence signal generated by the illumination light sheets, in imaging large vol...
Article
Full-text available
The avian egg is a closed system that protects the growing embryo from external factors but prevents direct observation of embryo development. Various culture systems exist in the literature to study the development of the embryo for short periods of incubation (from 12 h up to a maximum of 60 h of egg incubation). A common flaw to these culture te...
Preprint
Full-text available
Hyperspectral fluorescence imaging improves multiplexed observations of biological samples by utilizing multiple color channels across the spectral range to compensate for spectral overlap between labels. Typically, spectral resolution comes at a cost of decreased detection efficiency, which both hampers imaging speed and increases photo-toxicity t...
Article
Full-text available
Genetic mutations have long been recognized as drivers of cancer drug resistance, but recent work has defined additional non-genetic mechanisms of plasticity, wherein cancer cells assume a drug resistant phenotype marked by altered epigenetic and transcriptional states. Currently, little is known about the real-time, dynamic nature of this phenotyp...
Preprint
Full-text available
Domestication is associated with both morphological and behavioural phenotypic changes that differentiate domesticated species from their wild counterparts. Some of the traits are those purposely targeted by the selection process, whilst others co-occur as a result of selection. The combination of traits is referred to as the domestication syndrome...
Article
Full-text available
A sense of non-symbolic numerical magnitudes is widespread in the animal kingdom and has been documented in adult zebrafish. Here, we investigated the ontogeny of this ability using a group size preference (GSP) task in juvenile zebrafish. Fish showed GSP from 21 days post-fertilization and reliably chose the larger group when presented with discri...
Article
Full-text available
Significance Imaging of labeled excitatory synapses in the intact brain before and after classical conditioning permits a longitudinal analysis of changes that accompany associative memory formation. When applied to midlarval stage zebrafish, this approach reveals adjacent regions of synapse gain and loss in the lateral and medial pallium, respecti...
Preprint
Full-text available
The broad sharing of research data is widely viewed as of critical importance for the speed, quality, accessibility, and integrity of science. Despite increasing efforts to encourage data sharing, both the quality of shared data, and the frequency of data reuse, remain stubbornly low. We argue here that a major reason for this unfortunate state of...
Preprint
Full-text available
Visualizing cell shapes, interactions and lineages of differentiating cells is instrumental for understanding organ development and repair. Across species, strategies for stochastic multicolour labelling have greatly facilitated tracking cells in in vivo and mapping neuronal connectivity. Nevertheless, integrating multi-fluorophore information into...
Preprint
Organelle heterogeneity and inter-organelle associations within a single cell contribute to the limited sensitivity of current organelle separation techniques, thus hindering organelle subpopulation characterization. Here we use direct current insulator-based dielectrophoresis (DC-iDEP) as an unbiased separation method and demonstrate its capabilit...
Preprint
Full-text available
The expanded application of fluorescence imaging in biomedical and biological research towards more complex systems and geometries requires tools that can analyze a multitude of components at widely varying time- and length-scales. The major challenge in such complex imaging experiments is to cleanly separate multiple fluorescent labels with overla...
Preprint
Full-text available
Pancreatic β-cells respond to increased extracellular glucose levels by initiating a metabolic shift. That change in metabolism is part of the process of glucose-stimulated insulin secretion and is of particular interest in the context of diabetes. However, we do not fully understand how the coordinated changes in metabolic pathways and metabolite...
Article
Full-text available
We found a region of the zebrafish pallium that shows selective activation upon change in the numerosity of visual stimuli. Zebrafish were habituated to sets of small dots that changed in individual size, position, and density, while maintaining their numerousness and overall surface. During dishabituation tests, zebrafish faced a change in number...
Preprint
Full-text available
During adolescence, the lungs expand while alveoli increase greatly in number. A precise and deep understanding of the biological processes responsible for the many fold increase in alveoli during adolescence could form the foundation for novel treatments to reoptimize lung function after disease or injury. Herein we provide a unique insight into t...
Preprint
Full-text available
Increasing evidence of new-onset diabetes during the COVID19 pandemic indicates that the SARS-CoV2 virus may drive beta-cell dysfunction leading to diabetes, but it is unclear if it is a primary or secondary effect. Here, we present evidence of SARS-CoV-2 infection of pancreatic beta cells in vivo using a robust and reproducible non-human primates...
Article
Full-text available
Type 2 diabetes is characterized by β and α cell dysfunction. We used phasor-FLIM (Fluorescence Lifetime Imaging Microscopy) to monitor oxidative phosphorylation and glycolysis in living islet cells before and after glucose stimulation. In healthy cells, glucose enhanced oxidative phosphorylation in β cells and suppressed oxidative phosphorylation...
Article
The performance of light-field microscopy is improved by selectively illuminating the relevant subvolume of the specimen with a second objective lens. Here we advance this approach to a single-objective geometry, using an oblique one-photon illumination path or two-photon illumination to accomplish selective-volume excitation. The elimination of th...
Article
Full-text available
Fluorescence lifetime imaging microscopy (FLIM) with phasor analysis provides easy visualization and analysis of fluorophores' lifetimes which is valuable for multiple applications including metabolic imaging, STED imaging, FRET imaging and functional imaging. However, FLIM imaging typically suffers from low photon budgets, leading to unfavorable s...
Preprint
Full-text available
Non-symbolic number cognition based on an approximate sense of magnitude has been documented in adult zebrafish. Here we investigated the ontogeny of this ability using a group size preference task in juvenile zebrafish. Fish showed group size preference from 26 days post fertilization (dpf) and from 27 dpf fish reliably chose the larger group when...
Article
Full-text available
The gold standard of molecular pathogen detection is the quantitative polymerase chain reaction (qPCR). Modern qPCR instruments are capable of detecting 4–6 analytes in a single sample: one per optical detection channel. However, many clinical applications require multiplexing beyond this traditional single-well capacity, including the task of simu...
Article
Full-text available
Gold nanoparticles continue to generate interest for use in several biomedical applications. Recently, researchers have been focusing on exploiting their dual diagnostic/therapeutic theranostic capabilities. Before clinical translation can occur, regulatory agencies will require a greater understanding of their biodistribution and safety profiles p...
Preprint
Full-text available
Non-symbolic number cognition based on an approximate sense of magnitude has been documented in zebrafish. Here we investigated for the first time its neural bases. Zebrafish were habituated to a set of three or nine small dots associated with food reward. During habituation trials, the dots changed in their individual size, position and density ma...
Preprint
Full-text available
We present a novel approach for imaging the beating embryonic heart, based on combining two independent imaging channels to capture the full spatio-temporal information of the moving 3D structure. High-resolution, optically-sectioned image recording is accompanied by simultaneous acquisition of low-resolution, whole-heart recording, allowing the la...
Article
We present a novel approach for imaging the beating embryonic heart, based on combining two independent imaging channels to capture the full spatio-temporal information of the moving 3D structure. High-resolution, optically-sectioned image recording is accompanied by simultaneous acquisition of low-resolution, whole-heart recording, allowing the la...
Preprint
The performance of light-field microscopy is improved by selectively illuminating the relevant subvolume of the specimen with a second objective lens [1-3]. Here we advance this approach to a single-objective geometry, using an oblique one-photon illumination path or two-photon illumination to accomplish selective-volume excitation. The elimination...
Article
Full-text available
Light-sheet microscopy offers faster imaging and reduced phototoxicity in comparison to conventional point-scanning microscopy, making it a preferred technique for imaging biological dynamics for durations of hours or days. Such extended imaging sessions pose a challenge, as it reduces the number of specimens that can be imaged in a given day. Here...
Article
Full-text available
Evidence has shown that a variety of vertebrates, including fish, can discriminate collections of visual items on the basis of their numerousness using an evolutionarily conserved system for approximating numerical magnitude (the so-called Approximate Number System, ANS). Here we combine a habituation/dishabituation behavioural task with molecular...
Article
Full-text available
Light-field fluorescence microscopy uniquely provides fast, synchronous volumetric imaging by capturing an extended volume in one snapshot, but often suffers from low contrast due to the background signal generated by its wide-field illumination strategy. We implemented light-field-based selective volume illumination microscopy (SVIM), where illumi...
Article
Full-text available
Hyperspectral fluorescence imaging is gaining popularity for it enables multiplexing of spatio-temporal dynamics across scales for molecules, cells and tissues with multiple fluorescent labels. This is made possible by adding the dimension of wavelength to the dataset. The resulting datasets are high in information density and often require lengthy...
Article
Full-text available
Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased transcriptomics shows an upregulation of collagens...
Article
Full-text available
Metabolism is a key regulator of hematopoietic stem cell (HSC) functions. There is a lack of real-time, non-invasive approaches to evaluate metabolism in single HSCs. Using fluorescence lifetime imaging microscopy, we developed a set of metabolic optical biomarkers (MOBs) from the auto-fluorescent properties of metabolic coenzymes NAD(P)H and FAD....
Chapter
A more complete understanding of biological processes at cellular and molecular levels requires the ability to study them in time and space. Such observation became increasingly easy with the use of genetically encoded fluorescent markers, such as GFP, and the latest developments in optical microscopy. This combination of tools permits the structur...
Article
The hydraulic conductivity of the vitreous humor has been measured for the bovine eye. The experiment was carried out by placing it within upright cylindrical chamber, open at both ends, and letting its liquid content drain out of the bottom opening by gravity, through a 20μm nylon mesh filter. Additional negative pressure was provided at the exit...
Preprint
Light-sheet microscopy offers faster imaging and reduced phototoxicity in comparison to conventional point-scanning microscopy, making it a preferred technique for imaging biological dynamics for durations of hours or days. Such extended imaging sessions pose a challenge, as it reduces the number of specimens that can be imaged in a given day. Here