Biology subjects

Jung, W.

Publications and source records attributed to Jung, W..

25 records · Page 2Linked to original sources

bioRxiv2023

A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

The mammalian brain is composed of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. Here, we report a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain. The cell type atlas was created based on the combination of two single-cell-level, whole-brain-scale datasets: a single- cell RNA-sequencing (scRNA-seq) dataset of [~]7 million cells profiled, and a spatially resolved transcriptomic dataset of [~]4.3 million cells using MERFISH. The atlas is hierarchically organized into five nested levels of classification: 7 divisions, 32 classes, 306 subclasses, 1,045 supertypes and 5,200 clusters. We systematically analyzed the neuronal, non-neuronal, and immature neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell type organization in different brain regions, in particular, a dichotomy between the dorsal and ventral parts of the brain: the dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. We also systematically characterized cell-type specific expression of neurotransmitters, neuropeptides, and transcription factors. The study uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types across the brain, suggesting they mediate a myriad of modes of intercellular communications. Finally, we found that transcription factors are major determinants of cell type classification in the adult mouse brain and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole-mouse-brain transcriptomic and spatial cell type atlas establishes a benchmark reference atlas and a foundational resource for deep and integrative investigations of cell type and circuit function, development, and evolution of the mammalian brain.

neuroscience↗

bioRxiv2022

Evaluation of mouse behavioral responses to nutritive versus nonnutritive sugar using a deep learning-based 3D real-time pose estimation system

Animals are able to detect the nutritional content of sugar independently of taste. When given a choice between nutritive sugar and nonnutritive sugar, animals develop a preference for nutritive sugar over nonnutritive sugar during a period of food deprivation1-5. To quantify behavioral features during an episode of licking nutritive versus nonnutritive sugar, we implemented a multi-vision, deep learning-based 3D pose estimation system, termed the AI Vision Analysis for Three-dimensional Action in Real-Time (AVATAR)6. Using this method, we found that mice exhibit significantly different approach behavioral responses toward nutritive sugar versus nonnutritive sugar even before licking a sugar solution. Notably, the behavioral sequences during approach toward nutritive versus nonnutritive sugar became significantly different over time. These results suggest that the nutritional value of sugar not only promotes its consumption, but also elicits distinct repertoires of feeding behavior in deprived mice.

animal behavior and cognition↗

bioRxiv2022

Three-dimensional Interrogation of Cell Types and Instinctive Behavior in the Periaqueductal Gray

The periaqueductal gray (PAG) is a critical midbrain hub that relays information from the forebrain to motor and autonomic brainstem centers to orchestrate instinctive behaviors. The current organization of the PAG into four main radial columns lacks the resolution needed to account for the vast range of PAG functions. Using spatially resolved single-cell transcriptomic measurements, we uncovered widespread transcriptional heterogeneity in the PAG with >100 excitatory and inhibitory neuronal populations, which further assemble into 19 spatial metaclusters. We explored the transcriptional and spatial logic of PAG function during instinctive behaviors and demonstrated the regional recruitment of cell types for distinct behaviors. Unexpectedly, certain behaviors trigger differential spatial activation patterns within given cell types, illustrating the complexity of PAG molecular and functional 3D organization. The newly uncovered spatial motifs and high precision cellular map of instinctive behavior in the PAG open new avenues for a mechanistic understanding of PAG function.

neuroscience↗

bioRxiv2022

Effective Representation Learning via The Integrated Self-Supervised Pre-training models of StyleGAN2-ADA and DINO for Colonoscopy Images

In order to reach better performance in visual representation learning from image or video dataset, huge amount of annotated data are on demand. However, collecting and annotating large-scale datasets are costly and time-consuming tasks. Especially, in a domain like medical, it is hard to access patient images because of the privacy concerns and also not knowing what exactly to annotate without expert effort. One of the solutions to obviate the hassle is to use Self-Supervised learning methods (SSL) and Generative Adversarial Networks (GANs) together. SSL and GANs are quickly advancing fields. GANs have unique capability to create unlabeled data sources containing photo-realistic images while SSL methods are able to learn general image and video features from large-scale data without using any human-annotated labels. In this work, we explore leveraging the power of recently introduced StyleGAN2-ada and Self-Supervised Pre-Training of Dino together for the pretext task. Our underlying insight is also that leveraging the current approaches with Transfer Learning (TF) together brings benefit on doing pretext task in medical domain. By the strategy of unifying these two approaches, we propose the integrated version and use it derive representation learning on polyp dataset.

bioinformatics↗

bioRxiv2021

Development of spike receptor-binding domain nanoparticle as a vaccine candidate against SARS-CoV-2 infection in ferrets

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19 pandemic, enters host cells via the interaction of its Receptor-Binding Domain (RBD) of Spike protein with host Angiotensin-Converting Enzyme 2 (ACE2). Therefore, RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling H. pylori-bullfrog ferritin nanoparticles as an antigen delivery. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. 16-20 months-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD-nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD-nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss and clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious viruses in nasal washes and lungs as well as viral RNA in respiratory organs. This study demonstrates the Spike RBD-nanoparticle as an effective protein vaccine candidate against SARS-CoV-2.

immunology↗

bioRxiv2019

Mechanical stress compromises multicomponent efflux complexes in bacteria

Physical forces have long been recognized for their effects on the growth, morphology, locomotion, and survival of eukaryotic organisms1. Recently, mechanical forces have been shown to regulate processes in bacteria, including cell division2, motility3, virulence4, biofilm initiation5,6, and cell shape7,8, although it remains unclear how mechanical forces in the cell envelope lead to changes in molecular processes. In Gram-negative bacteria, multicomponent protein complexes that form rigid links across the cell envelope directly experience physical forces and mechanical stresses applied to the cell. Here we manipulate tensile and shear mechanical stress in the bacterial cell envelope and use single-molecule tracking to show that shear (but not tensile) stress within the cell envelope promotes disassembly of the tripartite efflux complex CusCBA, a system used by E. coli to resist copper and silver toxicity, thereby making bacteria more susceptible to metal toxicity. These findings provide the first demonstration that mechanical forces, such as those generated during colony overcrowding or bacterial motility through submicron pores, can inhibit the contact and function of multicomponent complexes in bacteria. As multicomponent, trans-envelope efflux complexes in bacteria are involved in many processes including antibiotic resistance9, cell division10, and translocation of outer membrane components11, our findings suggest that the mechanical environment may regulate multiple processes required for bacterial growth and survival.

biophysics↗

bioRxiv2018

Biphasic unbinding of Zur from DNA for transcription (de)repression in Live Bacteria

Transcription regulator on-off binding to DNA constitutes a mechanistic paradigm in gene regulation, in which the repressors/activators bind to operator sites tightly while the corresponding non-repressors/non-activators do not. Another paradigm regards regulator unbinding from DNA to be a unimolecular process whose kinetics is independent of regulator concentration. Using single-molecule single-cell measurements, we find that the behaviors of the zinc-responsive uptake regulator Zur challenges these paradigms. Apo-Zur, a non-repressor and presumed non-DNA binder, can bind to chromosome tightly in live E. coli cells, likely at non-consensus sequence sites. Moreover, the unbinding from DNA of its apo-non-repressor and holo-repressor forms both show a biphasic, repressed-followed-by-facilitated kinetics with increasing cellular protein concentrations. The facilitated unbinding likely occurs via a ternary complex formation mechanism; the repressed unbinding is first-of-its-kind and likely results from protein oligomerization on chromosome, in which an inter-protein salt-bridge plays a key role. This biphasic unbinding could provide functional advantages in Zur's facile switching between repression and derepression.

biophysics↗