Spatially resolved isotope tracing reveals tissue metabolic activity

Wang, Lin; Xi, Xing; Zeng, Xianfeng; Jackson, Susan; TeSlaa, Tara; Al‐Dalahmah, Osama; Samarah, Laith Z; Goodwin, Katharine; Yang, Lifeng; McReynolds, Melanie R.; Li, Xiaoxuan; Wolff, Jeremy J.; Rabinowitz, Joshua D.; Davidson, Shawn M.

doi:10.1038/s41592-021-01378-y

Cited by 89 publications

(80 citation statements)

References 28 publications

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“…Similarly, techniques like like IBEX [52] or Cell DIVE [53] have opened the door to spatial mapping of proteins in situ , making use of immunofluorescent imaging to detect protein-level spatial organization of cells and tissues [54]. Further, spatially-resolved isotope tracking has recently been used to quantify metabolic activity in various tissues, enabling direct observation of how tissues utilize specific compounds [55]. While most of these techniques capture data at a single time point, STRAINS enables real-time in situ , nondestructive spatiotemporal mapping and analysis of cell behavior in response to dynamic stimuli.…”

Section: Old Discussionmentioning

confidence: 99%

STRAINS: A Big Data Method for Classifying Cellular Response to Stimuli at the Tissue Scale

Zheng

Jackson

Fortier

et al. 2022

Preprint

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Cellular response to stimulation governs tissue scale processes ranging from growth and development to maintaining tissue health and initiating disease. To determine how cells coordinate their response to such stimuli, it is necessary to simultaneously track and measure the spatiotemporal distribution of their behaviors throughout the tissue. Here, we report on a novel in-situ Tissue Scale Cell Response Analysis (STRAINS) tool that uses fluorescent micrographs, cell tracking, and machine learning to measure such behavioral distributions. STRAINS is broadly applicable to any tissue where fluorescence can be used to indicate changes in cell behavior. For illustration, we use STRAINS to simultaneously analyze the mechanotransduction response of 5000 chondrocytes--over 20 million data points--in cartilage during the 50 ms to 4 hours after the tissue was subjected to local mechanical injury, known to initiate osteoarthritis. We find that chondrocytes exhibit a range of mechanobiological responses indicating activation of distinct biochemical pathways with clear spatial patterns related to the induced local strains during impact. These results illustrate the power of this approach.

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Section: Old Discussionmentioning

confidence: 99%

STRAINS: A Big Data Method for Classifying Cellular Response to Stimuli at the Tissue Scale

Zheng

Jackson

Fortier

et al. 2022

Preprint

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show abstract

“…Furthermore, MALDI is generally less quantitative and has less dynamic range than electrospray, which has led to its displacement in proteomics workflows. However, MALDI has roles in applications such as investigating drug distribution in tissues and tumors, and it can be combined with stable-isotope-labeled nutrient infusion (iso-imaging) to reveal the spatial organization of metabolic activity in tissues (Wang et al, 2022). Furthermore, MALDI is a promising technology for the analysis of single-cell metabolomes, where the aim is to characterize as much of the universe of small molecules (metabolites, lipids, etc.)…”

Section: Spatial Tissue Proteomics With Single-cell Resolutionmentioning

confidence: 99%

Unbiased spatial proteomics with single-cell resolution in tissues

2022

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“…In genetic mouse models of squamous cell carcinoma, MALDI MSI provided evidence for a subset of CD34+ cells containing increased glutathione abundance, conferring oxidative stress resistance and tumorigenic potential in vivo (Choi et al, 2021). MALDI MSI has pushed into isotope tracing with recent studies annotating metabolite labeling in regions of the mouse brain (Wang et al, 2022). It is still challenging to infer true metabolic flux, given the static nature of these experiments, but a wealth of comparisons can now be made in the same region.…”

Section: Spatially Resolved Metabolismmentioning

confidence: 99%