Spatial transcriptomics in bone research: navigating hype and hurdles

Spatial transcriptomics (ST) is a powerful technology that facilitates the measurement of gene expression levels within the native tissue architecture. Spatial-omics applications in musculoskeletal research have proven crucial in elucidating aspects of cellular heterogeneity, molecular mechanisms underlying injury, and gene expression patterning in tissue homeostasis and disease. However, the necessity for bone tissue decalcification and processing presents unique tissue-based challenges for the application of ST. Furthermore, ST intrinsic platform limitations, workflow bottlenecks, and analysis complications impose significant challenges to widespread utilisation. Here, we review current ST platforms and outline their respective advantages and limitations, discuss the current state of bone sample processing for use in omics-based approaches, and summarise basic bioinformatics considerations for downstream analysis. We describe how ST has been applied across different musculoskeletal tissues and animal models in the field so far ​and, finally, provide some potential future directions for the field in how ST ​approaches could be used to address lingering and future biological questions.