Spatial μProBe: a correlative multimodal imaging approach for spatial profiling of biological micro-environments

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Abstract

Despite fundamental advances in spatial omics, investigating cellular and molecular functions within their native environment remains a challenge in multiscale systems biology, especially in response to organ-level events. Here, we introduce Spatial µProBe (microProBe), a multimodal imaging approach for spatial profiling of biological micro-environments. Spatial µProBe enables preprocessing, registration and correlative analysis of 2D and 3D imaging modalities, supported by an intuitive user interface. As an application, we investigated bone mechanobiology and characterised the cellular and molecular responses to mechanical loading during adaptation and regeneration, which continuously regulate the local microarchitecture. By combining time-lapsed micro-computed tomography and spatial transcriptomics, we profiled the local mechanical in vivo environment of thousands of musculoskeletal cells and quantified their transcriptomic responses as a function of tissue strains and time. Spatial µProBe marks a crucial advance in the characterisation of multiscale tissues and signalling, facilitating the exploration of targeted molecular therapies for pathological conditions.

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