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Researchers at the Kennedy Institute have developed a new computational framework that allows simultaneous analysis of gene expression and mechanical forces within cells and tissues, uncovering insights into how the interplay between transcriptional and mechanical signals guides processes such as cell fate decisions or the formation of spatially distinct tissue compartments.

Representation of the spatial mechano-transcriptomics methodology, which allows spatial profiling of gene expression and mechanical forces at single cell resolution. © AI generated
Representation of the spatial mechano-transcriptomics methodology, which allows spatial profiling of gene expression and mechanical forces at single cell resolution.

Published in Nature Methods the new methodology integrates image-based spatial transcriptomics, which maps gene expression at single-cell resolution, with computational inference of the mechanical forces acting on individual cells across the the tissue. This allows the researchers to identify connections between the molecular programs controlling cell fate and the physical forces shaping tissues.

Lead researcher Adrien Hallou, Group Leader in Tissue Biology at the Kennedy Institute, said: ‘Spatial profiling technologies provide insights into how molecular programs are influenced by local signalling and environmental cues. However, cell fate specification and tissue patterning involve the interplay of biochemical and mechanical feedback. Therefore, to test for associations between them new methods were needed.

‘Our approach provides a window into the reciprocal relationship between gene regulation and mechanics in tissues, and by considering these factors together, we can gain a more holistic understanding of the mechanisms driving tissue morphogenesis during development, tissue maintenance at homeostasis or tissue architecture and function dysregulation in diseases.

 

Read the full story on the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences website.