Preclinical spatial transcriptomics study maps IMAT gene signature in cardiometabolic disease mouse model

This is a primary preclinical study using spatial transcriptomics to map human intermuscular adipose tissue (IMAT) gene signatures in a mouse model of diet-induced cardiometabolic disease. The scope includes cross-species comparison and functional experiments in human primary myoblasts with EBF2 overexpression.

Key findings indicate that IMAT expansion occurs within discrete stromal niches surrounding muscle fibers, characterized by coordinated activation of adipogenic, extracellular matrix, inflammatory, and metabolic pathways. Fibro-adipogenic progenitor (FAP) abundance does not predict adipocyte formation, supporting a model of localized and context-dependent lineage transitions. Cross-species comparison shows partial conservation of human IMAT gene programs, validating the mouse model while highlighting species-specific features. EBF2 is sufficient to induce adipogenic reprogramming in human primary myoblasts.

Limitations noted by the authors include that the preclinical mouse model may not fully replicate human disease, spatial transcriptomics findings are descriptive and require functional validation, and cross-species comparison shows partial conservation, indicating species-specific differences. No safety data or practice relevance are reported.

The study provides mechanistic insights into IMAT biology but is limited to preclinical models. Causality in humans is not established, and findings should not be overinterpreted for clinical outcomes without further validation.