Publications by authors named "Woong Sun"
Assessment of toxicity and efficacy in the nervous system is essential to ensure the safety of compounds and the efficacy of neurotherapeutics. Recently, technologies using neural organoids to mimic the structural and functional properties of human brain tissue have been developed to improve our understanding of human-specific brain development and to model neurodevelopmental disorders. This approach offers the potential for standardized toxicity testing and large-scale drug screening at the organ level.
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- The ligamentum flavum (LF) is essential for spinal stability, but its hypertrophy can lead to lumbar spinal canal stenosis (LSCS), with the underlying mechanisms not fully understood.
- The study explored cellular composition and signaling pathways in hypertrophied LF tissues obtained from patients with LSCS using single-cell RNA sequencing.
- Findings revealed that fibroblasts were the dominant cell type, with key signaling pathways identified that facilitate chronic inflammation and the trans-differentiation of fibroblasts into myofibroblasts, which may have implications for treating LSCS.
Article Synopsis
- * Research utilizing human pluripotent stem cells showed that VPA exposure affects neural stem cell development in a dose-dependent manner, causing more cell death during anterior neural differentiation and inhibiting cell growth during posterior differentiation.
- * Additionally, VPA exposure during posterior neural induction negatively impacts the morphogenesis of neural structures, indicating potential cytotoxic effects that could disrupt early embryonic neural development.
Article Synopsis
- Symmetry breaking is essential for accurate human development in organoids, influencing axis formation and spatial patterning.
- Self-organizing pluripotent stem cells can create variations in organoid structure, prompting the need for bioengineering techniques to ensure consistency.
- The review discusses how tools like micropatterns, microfluidics, and biomaterials aid in enhancing symmetry breaking, focusing on various organoid types and their physiological relevance.
Article Synopsis
- * Intrathecal (IT) delivery of AAV vectors can bypass some of these problems but has limitations in distribution and potential liver toxicity.
- * Researchers identified improved AAV capsids through testing in non-human primates, which demonstrated better retention in the spinal cord and lower distribution to the liver, making them promising candidates for spinal cord gene therapies compared to traditional AAV9.
Article Synopsis
- - This study provides a detailed overview of brain organoids, including expert insights and technical information on their definitions, characteristics, and culture methods, aimed at improving their use in research.
- - Brain organoids are 3D human cell models that replicate the nervous system, offering significant advantages over traditional 2D methods by mimicking anatomical structures and complex neuronal networks.
- - The research highlights the potential of brain organoids for studying nervous system development and cell interactions, enabling researchers to model diseases more effectively and overcome limitations of conventional culture methods.
Circadian coordination: understanding interplay between circadian clock and mitochondria.
Anim Cells Syst (Seoul)
May 2024
Article Synopsis
- Biological rhythms, especially circadian rhythms, are essential for regulating various processes in our bodies, helping us adapt to environmental changes.
- The circadian clock, found in nearly all cells, controls gene regulation linked to mitochondrial functions like energy production and structure.
- The review explores how mitochondrial rhythms may interact with or operate independently of the circadian clock, focusing on their cellular implications.
Article Synopsis
- - Fetal spinal cord ischemia can cause serious neurological issues but studying it has been difficult due to the lack of good experimental models.
- - The researchers created necrotic core-free human spinal cord organoids (nf-hSCOs) to test drugs for their effects on this condition, finding that using smaller organoids prevented complications from necrosis.
- - While many tested chemicals didn't show significant benefits, rapamycin was identified as a mild neuroprotective agent, making nf-hSCOs a promising model for studying fetal neural ischemia and screening potential treatments.
Article Synopsis
- Mitochondrial dysfunction plays a crucial role in chronic degenerative disorders, and immune responses triggered by mitochondrial DNA in the cytoplasm are significant.
- Researchers created targeted systems to induce double-strand breaks in mitochondrial DNA, resulting in a notable decrease in mtDNA copy numbers and increased interferon production in specific cell types.
- The study revealed that mitochondrial E3 ligase MARCH5 helps regulate immune responses by degrading active DNA-PKcs, preventing prolonged inflammation following mitochondrial damage.
Article Synopsis
- * The LAUNCHER system utilizes a modified tobacco etch virus protease and a blue-light-gated substrate to create a single-component switch that allows for precise release of biological payloads with minimal background noise.
- * LAUNCHER's versatility and ease of integration into synthetic circuits make it ideal for applications like gene expression and optochemogenetics, showcasing its value for enhanced performance in biological research.
Article Synopsis
- In vertebrates, the central nervous system develops from the neural tube through a process called neurulation, and defects in this process can lead to neural tube defects (NTDs).
- Recent research created human spinal cord organoids (hSCOs) to study neurulation and found that valproic acid (VPA) can induce defects in these organoids, affecting cell-cell junctional genes and proteins.
- The study also showed that VPA-treated mouse embryos had similar developmental issues, highlighting that hSCOs are useful for exploring the underlying molecular mechanisms of human neurulation and NTDs.
Article Synopsis
- - The development of fluorescent probes for mitochondria is common, but there's a need for less toxic options to better assess mitochondrial function.
- - A new cyanine-based NIR fluorescent probe, called T2, selectively targets mitochondria and has low toxicity by influencing the redox balance inside cells.
- - T2 also protects cortical neurons from cell death caused by oxidative stress, highlighting its potential as a safer imaging agent for mitochondria.
Salivary gland cells, which secrete water in response to neuronal stimulation, are closely connected to other neurons. Transcriptomic studies show that salivary glands also express some proteins responsible for neuronal function. However, the physiological functions of these common neuro-exocrine factors in salivary glands are largely unknown.
View Article and Find Full Text PDFSince its discovery in 2012, CRISPR Cas9 has been tried as a direct treatment approach to correct the causative gene mutation and establish animal models in neurodegenerative disorders. Since no strategy developed until now could completely cure Parkinson's disease (PD), neuroscientists aspire to use gene editing technology, especially CRISPR/Cas9, to induce a permanent correction in genetic PD patients expressing mutated genes. Over the years, our understanding of stem cell biology has improved.
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- - The study explores how symmetry breaking in human pluripotent stem cells (hPSCs) can mimic the processes of axis formation and cell patterning during development.
- - Researchers created polarized spinal cord organoids (pSCOs) that exhibit organized dorsoventral (DV) structures and can differentiate into specific cell types through the application of specific signals.
- - The control of dorsal/ventral domain proportions in pSCOs is achieved by adjusting the sizes of the initial cell micropatterns, resulting in distinct neural activities in mature organoids, which sheds light on the principles of neural development.
Article Synopsis
- The extracellular matrix (ECM) supports tissue structure and function but is complex and hard to study due to its insolubility.
- The research focused on decellularizing mouse brains to preserve their shape and ECM components, using a new method called O-CASPER combined with polymerization in oil.
- The decellularization successfully isolated key ECM proteins like collagen and laminin, indicating potential for future studies on brain and other tissues using this method.
Accurate spatiotemporal control of multicellular self-organization by various signaling pathways is essential for developmental stages. In particular, evolutionarily conserved Wnt signaling serves as a major morphogenetic switch to determine the anteroposterior axis of the embryo. Here, we developed a genetically encoded optochemogenetic Wnt switch, named optochemoWnt, by coupling a blue light-inducible CRY2olig and rapamycin-inducible LRP6c clustering.
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- Transparency of biological specimens is essential for creating detailed 3D images and understanding their structure and function.
- Traditional methods for achieving this transparency involve complex, multi-step protocols that are both time-consuming and complicated.
- This study developed a simplified, single-step procedure called MAX for refractive index adjustment, making it easier to clear tissues, especially those rich in extracellular matrix, while still allowing for additional processes to enhance transparency if needed.
Article Synopsis
- A study focused on improving the 3-D analysis of intraepidermal nerve fibers (IENFs) aims to enhance the assessment of peripheral neuropathies and skin disorders.
- The research utilized a suction blister method combined with a tissue-clearing technique, yielding better results than previous approaches for imaging IENFs.
- Key findings indicate specific 3-D parameters related to aging, which may serve as useful biomarkers for diagnosing complicated conditions affecting peripheral nerves and skin.
Three-dimensional imaging for the analysis of human epidermal melanocytes.
Pigment Cell Melanoma Res
September 2022
Three-dimensional (3-D) analysis of human epidermal melanocytes is required for deeper understanding of melanocytic disorders. The purpose of this study was to standardize 3-D imaging and quantification for the evaluation of epidermal melanocytes. The epidermal specimen was obtained using the suction blister method from a patient with melanocytic nevus on the forearm skin.
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- - The cerebral organoid (CO) model is valuable for studying neurodegenerative diseases but may not fully represent all clinical features seen in patients.
- - In this research, neurons derived from Alzheimer's patients' CO models showed reduced responsiveness to stimulation, which contradicted earlier findings.
- - The differences in neuron behavior may be influenced by the genetic background of the induced pluripotent stem cells, indicating the need for cautious interpretation of findings from the CO model in a clinical context.
Article Synopsis
- The study investigates the two proteins, CYFIP1 and CYFIP2, which have similar structures but different functions in the brain and are linked to various brain disorders.
- Experiments show that these proteins do not interact significantly with each other and have distinct distributions in brain cells, with CYFIP1 found in both neurons and astrocytes while CYFIP2 is primarily in neurons.
- Analysis of the proteins they interact with indicates that CYFIP1 is specifically associated with astrocytic focal adhesion, suggesting a unique role for CYFIP1 in brain function that differs from CYFIP2.
Chemical fluorescence-based dye staining for 3-dimensional histopathology analysis.
Anim Cells Syst (Seoul)
March 2022
Article Synopsis
- Tissue clearing is a technique used for 3D imaging in biomedical fields, particularly for examining human biopsy samples.
- Traditional immunofluorescence labeling for thicker samples is slow, making the use of low molecular weight dyes a promising alternative for faster and more effective labeling.
- The study identified specific dyes, like SYTO 16 combined with eosin and others for targeting collagen and brain structures, which significantly shorten the incubation time needed for 3D imaging.
The precise manipulation of the neural stem cell (NSC)-derived neural differentiation is still challenging, and there is a technological barrier to regulate the axonal regeneration in a controlled manner. Here, we developed a microfluidic chip integrated with a microelectrode array as an axonal guidance platform. The microfluidic electrode array chip consisted of two compartments and a bridge microchannel that could isolate and guide the axons.
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