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| Status |
Public on Oct 05, 2024 |
| Title |
Spatial Transcriptomics in Bone Mechanomics: Exploring the Mechanoregulation of Fracture Healing in the Era of Spatial Omics. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In recent decades, the field of bone mechanobiology has sought experimental techniques to unravel the molecular mechanisms governing the phenomenon of mechanically-regulated fracture healing. Each cell within a fracture site resides within different local micro-environments characterized by different levels of mechanical strain - thus, preserving the spatial location of each cell is critical in relating cellular responses to mechanical stimuli. Our spatial transcriptomics based “mechanomics” platform facilitates spatially-resolved analysis of the molecular profiles of cells with respect to their local in vivo mechanical environment by integrating time-lapsed in vivo micro-computed tomography, spatial transcriptomics, and micro-finite element analysis. We investigate the transcriptomic responses of cells as a function of the local strain magnitude by identifying the differential expression of genes in regions of high and low strain within a fracture site. Our platform thus has the potential to address fundamental open questions within the field and to discover mechano-responsive targets to enhance fracture healing.
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| Overall design |
Female 12-week-old mice (n = 4) received mid-diaphyseal femoral defects (0.68 ± 0.04 mm) using an established osteotomy surgical protocol. In vivo micro-CT imaging is performed weekly at the fracture site. Mice which exhibit bridging at 3 weeks post-surgery are then subdivided into Control and Loaded groups. Between weeks 3 – 5, mice receive either cyclic mechanical loading or sham-loading three times per week. All mice are euthanized at 5 weeks post-surgery. Spatial transcriptomics analyses are performed on the explanted femurs (n = 1 Control, n = 1 Loaded). Micro-finite element models - based upon in vivo micro-CT images - are used to generate tissue-scale 3D maps of the mechanical environment. We then correlated the molecular responses of individual cells to their local mechanical environment.
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| Web link |
https://doi.org/10.1126/sciadv.adp8496
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| Contributor(s) |
Mathavan N, Singh A, Marques FC, Günther D, Kuhn G, Wehrle E, Müller R |
| Citation(s) |
39742473 |
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| Submission date |
Apr 10, 2024 |
| Last update date |
Jan 02, 2025 |
| Contact name |
Neashan Mathavan |
| Organization name |
ETH Zurich
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| Department |
Institute for Biomechanics
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| Street address |
GLC H 21.1, Gloriastrasse 37 / 39
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| City |
Zurich |
| ZIP/Postal code |
8093 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1098722 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE263658_RAW.tar |
36.2 Mb |
(http)(custom) |
TAR (of CSV, JPG, JSON, MTX, PNG, TSV) |
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| Raw data are available in SRA |
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