Precision biomarker discovery powered by microscopy image fusion-assisted high spatial resolution ambient ionization mass spectrometry imaging

Lin, Li-En; Chen, Chih-Lin; Huang, Yun; Chung, Hsin-Hsiang; Lin, Chiao-Wei; Chen, Ko-Chien; Peng, Yu-Ju; Ding, Shih Torng; Wang, Mingyang; Shen, Tang‐Long; Hsu, Cheng-Chih

doi:10.1016/j.aca.2019.11.014

Cited by 35 publications

(46 citation statements)

References 66 publications

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“…A high voltage was applied to the syringe needle, and solvent was continuously perfused, such that a liquid microjunction formed between the capillaries at the sample surface. Desorbed lipids were then aspirated through the second capillary toward the mass spectrometer inlet, where electrospray ionization and subsequent detection occurred (30)(31)(32). NanoDESI-MS was performed in a negative ion mode at m/z 200-1,200, with methanol:acetonitrile:ethyl acetate 50:35:15 (vol/ vol/vol) as the solvent at 2.5 µL/min flow rate.…”

Section: Lipidomic Analysismentioning

confidence: 99%

Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells

et al. 2021

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BackgroundThere is increasing evidence that adipocytes play an active role in the cancer microenvironment. We have previously reported that adipocytes interact with acute lymphoblastic leukemia (ALL) cells, contributing to chemotherapy resistance and treatment failure. In the present study, we investigated whether part of this resistance is due to adipocyte provision of lipids to ALL cells.MethodsWe cultured 3T3-L1 adipocytes, and tested whether ALL cells or ALL-released cytokines induced FFA release. We investigated whether ALL cells took up these FFA, and using fluorescent tagged BODIPY-FFA and lipidomics, evaluated which lipid moieties were being transferred from adipocytes to ALL. We evaluated the effects of adipocyte-derived lipids on ALL cell metabolism using a Seahorse XF analyzer and expression of enzymes important for lipid metabolism, and tested whether these lipids could protect ALL cells from chemotherapy. Finally, we evaluated a panel of lipid synthesis and metabolism inhibitors to determine which were affected by the presence of adipocytes.ResultsAdipocytes release free fatty acids (FFA) when in the presence of ALL cells. These FFA are taken up by the ALL cells and incorporated into triglycerides and phospholipids. Some of these lipids are stored in lipid droplets, which can be utilized in states of fuel deprivation. Adipocytes preferentially release monounsaturated FFA, and this can be attenuated by inhibiting the desaturating enzyme steroyl-CoA decarboxylase-1 (SCD1). Adipocyte-derived FFA can relieve ALL cell endogenous lipogenesis and reverse the cytotoxicity of pharmacological acetyl-CoA carboxylase (ACC) inhibition. Further, adipocytes alter ALL cell metabolism, shifting them from glucose to FFA oxidation. Interestingly, the unsaturated fatty acid, oleic acid, protects ALL cells from modest concentrations of chemotherapy, such as those that might be present in the ALL microenvironment. In addition, targeting lipid synthesis and metabolism can potentially reverse adipocyte protection of ALL cells.ConclusionThese findings uncover a previously unidentified interaction between ALL cells and adipocytes, leading to transfer of FFA for use as a metabolic fuel and macromolecule building block. This interaction may contribute to ALL resistance to chemotherapy, and could potentially be targeted to improve ALL treatment outcome.

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Section: Lipidomic Analysismentioning

confidence: 99%

Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells

et al. 2021

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“…Interestingly, the study showed that the lipid distribution in different areas of the tissue was similar, independent of the species, suggesting lipid profiles are conserved across different species. Lin et al applied DESI and nanoDESI imaging combined with MALDI‐MSI and optical microscopy for the analysis of lipids and proteins in murine brain and kidney tissues and cancerous human tissues 118 . With a spatial resolution of 5 μm and 100 μm for DESI/nanoDESI and MALDI, respectively, the multimodal tissue imaging approach enabled improved precision in the determination of tumor margins, along with the detection of several new potential tumor biomarkers.…”

Section: Applications Of Ambient Ionization Mass Spectrometrymentioning

confidence: 99%

Applications of ambient ionization mass spectrometry in 2020: An annual review

Rankin‐Turner

Heaney

2021

Analytical Science Advances

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Recent developments in mass spectrometry (MS) analyses have seen a concerted effort to reduce the complexity of analytical workflows through the simplification (or removal) of sample preparation and the shortening of run‐to‐run analysis times. Ambient ionization mass spectrometry (AIMS) is an exemplar MS‐based technology that has swiftly developed into a popular and powerful tool in analytical science. This increase in interest and demonstrable applications is down to its capacity to enable the rapid analysis of a diverse range of samples, typically in their native state or following a minimalistic sample preparation approach. The field of AIMS is constantly improving and expanding, with developments of powerful and novel techniques, improvements to existing instrumentation, and exciting new applications added with each year that passes. This annual review provides an overview of applications of AIMS techniques over the past year (2020), with a particular focus on the application of AIMS in a number of key fields of research including biomedical sciences, forensics and security, food sciences, the environment, and chemical synthesis. Novel ambient ionization techniques are introduced, including picolitre pressure‐probe electrospray ionization and fiber spray ionization, in addition to modifications and improvements to existing techniques such as hand‐held devices for ease of use, and USB‐powered ion sources for on‐site analysis. In all, the information provided in this review supports the view that AIMS has become a leading approach in MS‐based analyses and that improvements to existing methods, alongside the development of novel approaches, will continue across the foreseeable future.

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“…However, the technique has not been extensively used for MSI analysis of hair, probably because of its relatively low spatial resolution. Recent advances have led to improved resolutions of between 20 and 100 µm [70,71], but the average diameter of adult human hair varies between 45 and 110 µm [18]. As the technique evolves towards improved resolution [70], it may find application in future hair analyses.…”

Section: Analysis Of Hair By Mass Spectrometry Imagingmentioning

confidence: 99%

“…Recent advances have led to improved resolutions of between 20 and 100 µm [70,71], but the average diameter of adult human hair varies between 45 and 110 µm [18]. As the technique evolves towards improved resolution [70], it may find application in future hair analyses.…”

Section: Analysis Of Hair By Mass Spectrometry Imagingmentioning

confidence: 99%

Mapping the Chemistry of Hair Strands by Mass Spectrometry Imaging—A Review

et al. 2021

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Hair can record chemical information reflecting our living conditions, and, therefore, strands of hair have become a potent analytical target within the biological and forensic sciences. While early efforts focused on analyzing complete hair strands in bulk, high spatial resolution mass spectrometry imaging (MSI) has recently come to the forefront of chemical hair-strand analysis. MSI techniques offer a localized analysis, requiring fewer de-contamination procedures per default and making it possible to map the distribution of analytes on and within individual hair strands. Applying the techniques to hair samples has proven particularly useful in investigations quantifying the exposure to, and uptake of, toxins or drugs. Overall, MSI, combined with optimized sample preparation protocols, has improved precision and accuracy for identifying several elemental and molecular species in single strands of hair. Here, we review different sample preparation protocols and use cases with a view to make the methodology more accessible to researchers outside of the field of forensic science. We conclude that—although some challenges remain, including contamination issues and matrix effects—MSI offers unique opportunities for obtaining highly resolved spatial information of several compounds simultaneously across hair surfaces.

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Precision biomarker discovery powered by microscopy image fusion-assisted high spatial resolution ambient ionization mass spectrometry imaging

Cited by 35 publications

References 66 publications

Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells

Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells

Applications of ambient ionization mass spectrometry in 2020: An annual review

Mapping the Chemistry of Hair Strands by Mass Spectrometry Imaging—A Review

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