Biology subjects

Mizoguchi, S.

Publications and source records attributed to Mizoguchi, S..

4 recordsLinked to original sources

bioRxiv2026

Epithelial Reprogramming and Transition during Pulmonary Bioengineering

Recent research has emphasized the critical role of cell state transitions in tissue homeostasis. In lung biology, transitional cells are recognized as a feature of tissue-scale processes during both normal physiology and disease. The precise way that transitional cell states emerge and are regulated remains to be determined. Engineered tissues, built in a laboratory through bioengineering approaches, allow detailed study of cellular states that are not commonly found in native biology, and allow opportunities to directly induce and manipulate cellular transitions. The following study explores and characterizes epithelial cell states that emerge via cellular reprogramming in a tissue engineering context. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/701406v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@1d456f3org.highwire.dtl.DTLVardef@1989ba5org.highwire.dtl.DTLVardef@127dd7org.highwire.dtl.DTLVardef@3dd7a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

A Tunable Pulmonary Organoid Model Demonstrates Compositionally Driven Epithelial Plasticity and Immune Polarization

Summary/AbstractAberrant epithelial regeneration and immune remodeling are hallmarks of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), COPD, and post-viral syndromes. Yet how cellular context shapes these trajectories remains unresolved. We present a tunable, primary rat-derived lung organoid model that systematically varies immune, epithelial, and mesenchymal inputs to reveal how composition alone dictates epithelial plasticity and macrophage polarization. Across organoid conditions that varied by relative starting lineage ratios, we observed the spontaneous emergence of disease-relevant transitional cell states, including Sox9+ stressed progenitors, RAS-like intermediates, and hillock-like cells, alongside distinct macrophage activation profiles. In mesenchyme-rich contexts, epithelial-immune-mesenchymal crosstalk appeared to reinforce inflammatory signaling and stabilize transitional persistence, while immune-dominant inputs favored ATI-like repair and squamous remodeling. Hillock-like cells displayed context-specific polarization and expressed immune-regulatory genes, suggesting a role as epithelial orchestrators that help calibrate inflammatory response during regeneration. Connectomic analysis via NICHES revealed that regenerative outcomes were associated with dynamic multicellular signaling networks that integrate stress sensing, immune coordination, and epithelial resilience. This platform provides a tractable system for modeling milieu-specific repair and regenerative mechanisms and could inform therapeutic strategies aimed at redirecting epithelial fate in chronic lung disease.

bioengineering↗

bioRxiv2024

Engineered Whole Lungs for Tissue Biology

End-stage lung disease and lung cancer significantly contribute to global mortality, necessitating new research strategies for studying pulmonary biology. Here, we present an engineered whole-lung tissue model used to evaluate the effects of cellular communities on tissue organization and alveolar barrier function. Engineered lungs were grown ex vivo on decellularized whole-lung matrices as structurally biomimetic, bioactive scaffolds. Histologic architecture of engineered lungs improved with the addition of alveolar macrophages, coming to resemble neonatal lung. Incorporating alveolar macrophages maximized the differentiation of native-like cellular communities, including alveolar type I-like epithelium, bronchioalveolar stem cells, microvascular endothelium, and pericytes. Cell-cell signaling in engineered lungs showed activation of developmental and inflammatory pathways, including WNT, Notch, and FGF signaling pathways. Engineered lungs containing alveolar macrophages showed a 668% improvement in measured alveolar barrier function. This work demonstrates the potential utility of engineered lung models for studying principles of tissue biology and pulmonary regeneration.

bioengineering↗

bioRxiv2024

Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration

Tissue homeostasis is controlled by cellular circuits governing cell growth, organization, and differentation. In this study we identify previously undescribed cell-to-cell communication that mediates information flow from mechanosensitive pleural mesothelial cells to alveolar-resident stem-like tuft cells in the lung. We find mesothelial cells to express a combination of mechanotransduction genes and lineage-restricted ligands which makes them uniquely capable of responding to tissue tension and producing paracrine cues acting on parenchymal populations. In parallel, we describe a large population of stem-like alveolar tuft cells that express the endodermal stem cell markers Sox9 and Lgr5 and a receptor profile making them uniquely sensitive to cues produced by pleural Mesothelium. We hypothesized that crosstalk from mesothelial cells to alveolar tuft cells might be central to the regulation of post-penumonectomy lung regeneration. Following pneumonectomy, we find that mesothelial cells display radically altered phenotype and ligand expression, in a pattern that closely tracks with parenchymal epithelial proliferation and alveolar tissue growth. During an initial pro-inflammatory stage of tissue regeneration, Mesothelium promotes epithelial proliferation via WNT ligand secretion, orchestrates an increase in microvascular permeability, and encourages immune extravasation via chemokine secretion. This stage is followed first by a tissue remodeling period, characterized by angiogenesis and BMP pathway sensitization, and then a stable return to homeostasis. Coupled with key changes in parenchymal structure and matrix production, the cumulative effect is a now larger organ including newly-grown, fully-functional tissue parenchyma. This study paints Mesothelial cells as a key orchestrating cell type that defines the boundary of the lung and exerts critical influence over the tissue-level signaling state regulating resident stem cell populations. The cellular circuits unearthed here suggest that human lung regeneration might be inducible through well-engineered approaches targeting the induction of tissue regeneration and safe return to homeostasis.

systems biology↗