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Spatial Transcriptomics Inc platform geomx digital spatial profiler
A PULSE-CHASE iSILK paradigm. Experimental Design 1: PULSE period ( 15 N diet) between 6-10 months of age. Experimental Design 2: PULSE period between 6-10 months of age, CHASE period ( 14 N diet) between 10–18 months of age. Resulting Aβ1-42 MALDI MS isotopologue pattern that is right-shifted (Δm) due to increasing 15 N incorporation. B Representative images of plaque load from <t>GeoMx</t> whole slide scans, repeated on four independent whole-brain slices at 18-months and three at 10-months. C MALDI MSI single ion image of Aβ1-42 in cortex section. D Schematic overview of the correlative hyperspectral imaging and MALDI MSI experiment. 15 N enrichment (nitrogen index) was calculated as the AUC ratio of the 4th to 3rd peak in the Aβ1-42 isotopologue pattern. Higher values indicate greater 15 N incorporation. E Schematic overview of the correlative <t>spatial</t> <t>transcriptomics</t> (GeoMx) and MALDI MSI experiment. Stable 15 N enrichments (nitrogen index) corresponding to plaque age was calculated by extracting the FWHM of the Aβ1-42 peak, where a broader peak indicates increased 15 N incorporation and higher age. F Schematic overview of the validation experiment. Plaque morphology was evaluated by LCO hyperspectral imaging. IHC of selected proteins were correlated with plaque age, as evaluated by hyperspectral imaging. G Representative spectra from MALDI MSI showing the 14 N and 15 N-enriched Aβ1-42 m/z peak. H Aβ1-42 mass analysis comparing the plaque center (Cen) vs. the periphery (Peri) in 10-month-old mice ( p = 0.00017), ( I ) in 18-month-old mice ( p = 0.00000077), and ( J ) differences between cortex and hippocampus ( p = 0.022). H , I Linear Mixed Model accounting for across animals and repeated measures, point color indicates animal, 15 replicates over n = 3 m mice and 22 replicates over n = 4 m mice, respectively. J Two-sided Paired t-test, 22 replicates over n = 4 m mice, data presented as mean ± SEM. K Representative MALDI MSI image of 15 N and 14 N enriched Aβ1-42 distribution in plaques in 18-month-old mice. Parts of the figure created in BioRender. Szadziewska, A. ( https://BioRender.com/4qpojxz ) Image in ( E ) provided by Bruker Spatial Biology. Significance levels: *** P < 0.001, ** P < 0.01; * P < 0.05. Source data are provided as a Source Data file. FWHM full width at half maximum, RP reflector mode, LP linear mode.
Platform Geomx Digital Spatial Profiler, supplied by Spatial Transcriptomics Inc, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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A PULSE-CHASE iSILK paradigm. Experimental Design 1: PULSE period ( 15 N diet) between 6-10 months of age. Experimental Design 2: PULSE period between 6-10 months of age, CHASE period ( 14 N diet) between 10–18 months of age. Resulting Aβ1-42 MALDI MS isotopologue pattern that is right-shifted (Δm) due to increasing 15 N incorporation. B Representative images of plaque load from GeoMx whole slide scans, repeated on four independent whole-brain slices at 18-months and three at 10-months. C MALDI MSI single ion image of Aβ1-42 in cortex section. D Schematic overview of the correlative hyperspectral imaging and MALDI MSI experiment. 15 N enrichment (nitrogen index) was calculated as the AUC ratio of the 4th to 3rd peak in the Aβ1-42 isotopologue pattern. Higher values indicate greater 15 N incorporation. E Schematic overview of the correlative spatial transcriptomics (GeoMx) and MALDI MSI experiment. Stable 15 N enrichments (nitrogen index) corresponding to plaque age was calculated by extracting the FWHM of the Aβ1-42 peak, where a broader peak indicates increased 15 N incorporation and higher age. F Schematic overview of the validation experiment. Plaque morphology was evaluated by LCO hyperspectral imaging. IHC of selected proteins were correlated with plaque age, as evaluated by hyperspectral imaging. G Representative spectra from MALDI MSI showing the 14 N and 15 N-enriched Aβ1-42 m/z peak. H Aβ1-42 mass analysis comparing the plaque center (Cen) vs. the periphery (Peri) in 10-month-old mice ( p = 0.00017), ( I ) in 18-month-old mice ( p = 0.00000077), and ( J ) differences between cortex and hippocampus ( p = 0.022). H , I Linear Mixed Model accounting for across animals and repeated measures, point color indicates animal, 15 replicates over n = 3 m mice and 22 replicates over n = 4 m mice, respectively. J Two-sided Paired t-test, 22 replicates over n = 4 m mice, data presented as mean ± SEM. K Representative MALDI MSI image of 15 N and 14 N enriched Aβ1-42 distribution in plaques in 18-month-old mice. Parts of the figure created in BioRender. Szadziewska, A. ( https://BioRender.com/4qpojxz ) Image in ( E ) provided by Bruker Spatial Biology. Significance levels: *** P < 0.001, ** P < 0.01; * P < 0.05. Source data are provided as a Source Data file. FWHM full width at half maximum, RP reflector mode, LP linear mode.

Journal: Nature Communications

Article Title: Isotope-encoded spatial biology identifies plaque-age-dependent maturation and synaptic loss in an Alzheimer’s disease mouse model

doi: 10.1038/s41467-025-63328-y

Figure Lengend Snippet: A PULSE-CHASE iSILK paradigm. Experimental Design 1: PULSE period ( 15 N diet) between 6-10 months of age. Experimental Design 2: PULSE period between 6-10 months of age, CHASE period ( 14 N diet) between 10–18 months of age. Resulting Aβ1-42 MALDI MS isotopologue pattern that is right-shifted (Δm) due to increasing 15 N incorporation. B Representative images of plaque load from GeoMx whole slide scans, repeated on four independent whole-brain slices at 18-months and three at 10-months. C MALDI MSI single ion image of Aβ1-42 in cortex section. D Schematic overview of the correlative hyperspectral imaging and MALDI MSI experiment. 15 N enrichment (nitrogen index) was calculated as the AUC ratio of the 4th to 3rd peak in the Aβ1-42 isotopologue pattern. Higher values indicate greater 15 N incorporation. E Schematic overview of the correlative spatial transcriptomics (GeoMx) and MALDI MSI experiment. Stable 15 N enrichments (nitrogen index) corresponding to plaque age was calculated by extracting the FWHM of the Aβ1-42 peak, where a broader peak indicates increased 15 N incorporation and higher age. F Schematic overview of the validation experiment. Plaque morphology was evaluated by LCO hyperspectral imaging. IHC of selected proteins were correlated with plaque age, as evaluated by hyperspectral imaging. G Representative spectra from MALDI MSI showing the 14 N and 15 N-enriched Aβ1-42 m/z peak. H Aβ1-42 mass analysis comparing the plaque center (Cen) vs. the periphery (Peri) in 10-month-old mice ( p = 0.00017), ( I ) in 18-month-old mice ( p = 0.00000077), and ( J ) differences between cortex and hippocampus ( p = 0.022). H , I Linear Mixed Model accounting for across animals and repeated measures, point color indicates animal, 15 replicates over n = 3 m mice and 22 replicates over n = 4 m mice, respectively. J Two-sided Paired t-test, 22 replicates over n = 4 m mice, data presented as mean ± SEM. K Representative MALDI MSI image of 15 N and 14 N enriched Aβ1-42 distribution in plaques in 18-month-old mice. Parts of the figure created in BioRender. Szadziewska, A. ( https://BioRender.com/4qpojxz ) Image in ( E ) provided by Bruker Spatial Biology. Significance levels: *** P < 0.001, ** P < 0.01; * P < 0.05. Source data are provided as a Source Data file. FWHM full width at half maximum, RP reflector mode, LP linear mode.

Article Snippet: The spatial transcriptomics platform GeoMx® Digital Spatial Profiler was selected over other sequencing techniques due to its ability to target plaque-specific gene expression changes, offering a more spatially resolved technique for AD pathology-associated alterations compared to the more commonly used RNA sequencing methods .

Techniques: Pulse Chase, Imaging, Biomarker Discovery