Biology subjects

Yokota, J.

Publications and source records attributed to Yokota, J..

3 recordsLinked to original sources

bioRxiv2025

Basement membrane components define the microenvironment of aggregated fibroblasts in the skin and support their aggregation in vitro

The dermal papilla (DP), a specialized fibroblast aggregate in mammalian skin, plays a pivotal role in hair follicle development and regeneration through epithelial-mesenchymal interactions. While its aggregated configuration is critical for its function, the mechanism maintaining this organization has remained unclear. Here, we show that human DP cells are embedded in a basement membrane (BM)-like extracellular matrix (ECM) rather than in conventional interstitial fibrillar ECM, such as collagen I. This BM-like ECM occupies the intercellular space as a diffuse, mesh-like structure, with minimal cell-cell adhesion. These fibroblasts interact with specific laminin isoforms containing 1, 2 or 4 chains via integrin 7{beta}1, resulting in weak adhesiveness. In vitro, DP spheroids remained aggregated in a BM extract-based matrix, Matrigel, but dispersed in collagen I gel in an 1{beta}1 integrin-dependent manner. Our findings suggest that the BM components within DP aggregates mediate cell-ECM interactions and maintain the cohesive DP structure in the absence of strong cell-cell contacts. These results reveal an unconventional role for the BM as an adhesive microenvironment that sustains fibroblast aggregation and offer a new perspective on mesenchymal tissue organization and in vitro culture substrates for DP cells.

cell biology↗

bioRxiv2025

Computed Tomography-Derived Elastic Modulus as a Noninvasive Marker of Aortic Wall Integrity: Correlation with Histopathology in the Ascending Aorta

BackgroundAscending aortic aneurysms and dissections are life-threatening conditions often requiring prophylactic surgeries. Current guidelines rely primarily on aortic diameter for intervention; however, many dissections occur without severe dilation. Mechanical properties, such as elastic modulus have emerged as potential predictors of disease progression; nonetheless, noninvasive clinical applications remain limited. This study evaluated the relationship between the computed tomography (CT)-derived elastic modulus of the ascending aorta and the histopathological characteristics of the aortic media. MethodsThirty patients who underwent surgical ascending aorta replacement were included in this study. Preoperative CT was used to calculate the aortic elastic modulus based on geometric measurements and pulse pressure. Resected aortic specimens were subjected to histological and immunohistochemical analyses to assess elastin, collagen, vascular smooth muscle cells (VSMCs), and smoothelin expression. Correlation analyses between the CT-derived elastic modulus and aortic media composition were conducted after adjusting for age and aortic diameter. ResultsThe CT-derived elastic modulus exhibited a significant negative correlation with elastin area and a positive correlation with collagen area. Additionally, a moderate negative correlation was observed between the elastic modulus and elastin fiber waviness. A strong negative correlation was detected between the elastic modulus and the proportion of contractile-type (smoothelin-positive) VSMCs. These findings remained significant after adjusting for confounders. ConclusionsCT-derived elastic modulus of the ascending aorta reflects the underlying pathological changes, including extracellular matrix remodeling and VSMC phenotypic modulation. Noninvasive assessment of aortic mechanical properties may provide novel insights into aortic disease progression and therapeutic responses.

pathology↗

bioRxiv2020

ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer

Immunotherapies provide effective treatments for previously untreatable tumors and identifying tumor-specific epitopes can help elucidate the molecular determinants of therapy response. Here, we describe a pipeline, ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer), for the comprehensive identification of tumor-specific splicing-derived epitopes. Using RNA sequencing and mass spectrometry for MHC-I associated proteins, ISOTOPE identified neoepitopes from tumor-specific splicing events that are potentially presented by MHC-I complexes. Analysis of multiple samples indicates that splicing alterations may affect the production of self-epitopes and generate more candidate neoepitopes than somatic mutations. Although there was no difference in the number of splicing-derived neoepitopes between responders and non-responders to immune therapy, higher MHC-I binding affinity was associated with a positive response. Our analyses highlight the diversity of the immunogenic impacts of tumor-specific splicing alterations and the importance of studying splicing alterations to fully characterize tumors in the context of immunotherapies. ISOTOPE is available at https://github.com/comprna/ISOTOPE Author summaryImmune cells have the ability to attack tumor cells upon the identification of tumor-specific peptides, i.e., epitopes, that are presented by the major histocompatibility complex (MHC). New cancer immunotherapies that help trigger this process provide a promising therapeutic strategy. One crucial aspect for their success is the ability to determine the molecular properties of a tumor that are informative about the effectiveness of the therapy. Alterations in the way genes are processed to express RNA molecules could lead to the production of new peptides, with some of them potentially being presented as tumor epitopes and facilitate the attack of immune cells. It is therefore essential to facilitate the identification of these splicing-derived epitopes. In this work, we describe a computational pipeline that performs a comprehensive identification of splicing alterations in a tumor and the potential epitopes that they would produce. Analysis of tumor samples with our pipeline show that responders and non-responders to immune therapy do not show differences in the number of splicing-derived epitopes, but splicing neoepitopes have higher affinity to the MHC complex in responders. Our new pipeline facilitates the genome-scale analysis of the role of splicing alterations in shaping the molecular properties that influence response to immunotherapy.

bioinformatics↗