Biology subjects

Matsuyama, T.

Publications and source records attributed to Matsuyama, T..

5 recordsLinked to original sources

bioRxiv2025

Pathological Angiogenesis Precedes the Onset of Aortic Dissection

Aortic dissection (AD) is a severe, life-threatening disease that occurs abruptly1. Although remodeling and inherent vulnerability of the aortic media, as observed in heritable connective tissue disorders such as Marfan syndrome, have been implicated in the onset of AD, the precise pathological mechanisms underlying the non-heritable form, which accounts for most cases, remains largely unknown2. Here, using hyperacute AD patient-derived samples, we show that pathological angiogenesis within the aortic media precedes the onset of dissection. Integrating single-cell transcriptomic analysis of aortic medial endothelial cells with high-resolution imaging revealed temporal changes preceding dissection. Hypoxic alterations in the media triggered osteochondrogenic changes in smooth muscle cells, promoted hydroxyapatite deposition, and induced angiogenesis via VEGF secretion from AD-specific CD14+CD68+CD163+MRC1(CD206)neg-low macrophages. Atomic force microscopy revealed that these processes culminated in the formation of a soft capillary layer, potentially concentrating stress on this region and contributing to AD onset. H&E staining of archived specimens revealed that non-heritable AD can be classified into angiogenic or non-angiogenic subtypes, with more than half exhibiting the former. In contrast, acute AD cases associated with Marfan syndrome typically exhibit a non-angiogenic pattern, suggesting distinct underlying mechanisms. This study reports angiogenesis as a key pathological driver in non-heritable AD and highlight potential targets for early diagnosis, prevention, and treatment.

pathology↗

bioRxiv2025

Hidden Markov Models Reveal Behavioral State Dynamics in Depth-Related Locomotion in Mice

Understanding how mice process and respond to visual depth cues is crucial for studying visual perception, yet traditional behavioral analyses often miss key aspects of this process, such as the dynamic transitions between behavioral states, the influence of environmental context, and the integration of multiple spatial cues that shape depth-related behaviors. Here we demonstrate that mouse responses to visual depth cues are more sophisticated than previously recognized, involving both direct avoidance behaviors and complex modulations of exploratory patterns. By combining a modified circular apparatus with Hidden Markov Model analysis, we reveal that mice transition between three distinct behavioral states--resting, exploring, and navigating--in response to visual depth cues. Using this framework, we uncover several fundamental aspects of mouse visual processing: depth perception has an optimal range of spatial frequencies, with strongest responses to patterns between 6-8 cm; visual processing integrates multiple spatial cues rather than triggering simple avoidance; and initial strong cliff-avoidance responses evolve into more nuanced behavioral adaptations over time. Comparisons between wild-type C57BL/6J mice (Mus musculus), retinal degeneration models (rd1-2J, C57BL/6J background, Mus musculus), and control conditions confirm that these behavioral patterns specifically reflect visual processing rather than general exploratory behavior. These findings reveal that mouse depth perception involves sophisticated neural processing that modulates overall exploratory behavior rather than simply triggering avoidance responses. Our approach establishes a new framework for analyzing complex behavioral sequences in neuroscience research, demonstrating how refined behavioral analysis can reveal previously undetectable aspects of sensory processing.

animal behavior and cognition↗

bioRxiv2024

The Brain Tells a Story: Unveiling Distinct Representations of Semantic Content in Speech, Objects, and Stories in the Human Brain with Large Language Models

In recent studies, researchers have used large language models (LLMs) to explore semantic representations in the brain; however, they have typically assessed different levels of semantic content, such as speech, objects, and stories, separately. In this study, we recorded brain activity using functional magnetic resonance imaging (fMRI) while participants viewed 8.3 hours of dramas and movies. We annotated these stimuli at multiple semantic levels, which enabled us to extract latent representations of LLMs for this content. Our findings demonstrate that LLMs predict human brain activity more accurately than traditional language models, particularly for complex background stories. Furthermore, we identify distinct brain regions associated with different semantic representations, including multi-modal vision-semantic representations, which highlights the importance of modeling multi-level and multi-modal semantic representations simultaneously. We will make our fMRI dataset publicly available to facilitate further research on aligning LLMs with human brain function. Please check out our webpage at https://sites.google.com/view/llm-and-brain/.

neuroscience↗

bioRxiv2022

Self-organization, quality control, and preclinical studies of human iPSC-derived retinal sheets for tissue-transplantation therapy

Three-dimensional retinal organoids (3D-retinas) are a promising graft source for transplantation therapy. We previously developed self-organizing culture for 3D-retina generation from human pluripotent stem cells (hPSCs). Here we present a quality control method and preclinical studies for tissue-sheet transplantation. Self-organizing hPSCs differentiated into both retinal and off-target tissues. Gene expression analyses identified the major off-target tissues as eye-related, cortex-like, and spinal cord-like tissues. For quality control, we developed a qPCR-based test in which each hPSC-derived neuroepithelium was dissected into two tissue-sheets: inner-central sheet for transplantation and outer-peripheral sheet for qPCR to ensure retinal tissue selection. During qPCR, tissue-sheets were stored for 3-4 days using a newly developed preservation method. In a rat tumorigenicity study, no transplant-related adverse events were observed. In retinal degeneration model rats, retinal transplants differentiated into mature photoreceptors and exhibited light responses in electrophysiology assays. These results demonstrate our rationale toward self-organizing retinal sheet transplantation therapy.

neuroscience↗

bioRxiv2020

Genetically engineered retina for improved retinal reconstruction after transplantation

ES/iPS-retinal sheet transplantation, which supplies photoreceptors as well as other retinal cells, has been shown able to restore visual function in mice with end-stage retinal degeneration. Here, by introducing a novel type of genetically engineered ES/iPS-retinal sheet with reduced numbers of secondary retinal neurons but intact photoreceptor cell layer structure, we reinforced the evidence that ES/iPS-retinal sheet transplantation can establish synaptic connections with the host, restore light responsiveness and reduce aberrant RGC spiking. Furthermore, we show that genetically engineered grafts can substantially improve the outcome of the treatment by improving neural integration. We speculate that this leads to reduced spontaneous activity in the host which in turn contributes to a better visual recovery.

neuroscience↗