Mitochondrial clone tracing within spatially intact human tissues.

Understanding tissue development and intra-tissue evolution requires the ability to trace clones in intact tissues coupled with high-plex molecular profiling preserving spatial context. However, current lineage tracing tools are incompatible with spatial omics. Here, we present SUMMIT (Spatially Unveiling Mitochondrial Mutations In Tissues), a spatially-resolved lineage tracing technology that integrates gene expression profiling with mitochondrial mutation-based clone identification.

Mitochondrial dysfunction drives basal cell hyperplasia in eosinophilic oesophagitis.

Background: Eosinophilic oesophagitis (EoE) is a food allergen-induced inflammatory disorder characterised by interleukin (IL)-13-mediated oesophageal inflammation and epithelial basal cell hyperplasia (BCH). The role of mitochondria in EoE pathogenesis remains elusive.

Design: Prompted by single cell transcriptomics data, we interrogated the role of mitochondria in EoE pathobiology using patient biopsies, EoE-mouse models and oesophageal epithelial cells grown in monolayer and three-dimensional (3D) organoid cultures treated with EoE-relevant cytokines.

FOXM1 Modulation Alleviates Epithelial Remodeling and Inflammation in Eosinophilic Esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic allergic disease characterized by esophageal epithelial remodeling, barrier dysfunction, and inflammation. Despite histologic remission, molecular and structural changes in the epithelium persist, contributing to ongoing symptoms and relapse. The transcription factor FOXM1 has been shown to be a key regulator of epithelial proliferation and inflammation in allergic asthma.