Biotechnology Bulletin ›› 2021, Vol. 37 ›› Issue (1): 32-51.doi: 10.13560/j.cnki.biotech.bull.1985.2020-1374
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YIN Zhi-bin1(), HUANG Wen-jie1, WU Xin-zhou2(), YAN Shi-juan1()
Received:
2020-11-12
Online:
2021-01-26
Published:
2021-01-15
Contact:
WU Xin-zhou,YAN Shi-juan
E-mail:zbyin@agrogene.ac.cn;wuxz@scau.edu.cn;shijuan@agrogene.ac.cn
YIN Zhi-bin, HUANG Wen-jie, WU Xin-zhou, YAN Shi-juan. Spatially Resolved Metabolomics:Progress and Challenges[J]. Biotechnology Bulletin, 2021, 37(1): 32-51.
Year | Species | Lateral resolution | Imaging techniques | Nos. of metabolites | Imaging analytes | Involved pathway | Ref. |
---|---|---|---|---|---|---|---|
Animal Tissue Imaging | |||||||
2019 | Prostate cancer tissue | 150 μm | DESI | 25 | Phospholipids,fatty acids,and organic acids | Fatty acid and lipid biosynthesis | [64] |
2019 | Whole-body rat tissue sections | 500 μm | AFADESI | 17 | Epimeric drugs,neurotransmitters(GABA,glutamic acid,and glutamine) | Metabolic pathway of drugs | [65] |
2019 | Esophageal squamous cell carcinoma tissue | 200 μm | AFADESI | 27 | Amino acids,pyrimidines,fatty acids,saccharides,phospholipids,and organic acids | Proline/fatty acid/ polyamine biosynthesis,and glutamine/uridine/ histidine metabolism | [15] |
2020 | Breast cancer tissue | 100 μm | MALDI | 24 | Carnitines and long-chain acylcarnitines | Carnitine system-mediated fatty acid β-oxidation pathway | [62] |
2020 | Rat kidney tissue | 200 μm | AFADESI | 38 | Aristolochic acid I,amino acids,lipids,inosine,adenosine triphosphate,and carnitine | Arginine-creatinine metabolic pathway,urea cycle,and serine biosynthesis | [64] |
Plant Tissue Imaging | |||||||
2008 | Arabidopsis thaliana leaves | 200 μm | MALDI | 3 | Glucosinolates | Location of glucosinolates within a leaf regarding plant defenses | [79] |
2012 | Gossypium hirsutum seed | 50 μm | MALDI | 69 | TAGs,PAs,PEs,PCs,β-sitosterol,and polyphenolic gossypol | Location of TAGs and PCs in cotton embryos | [13] |
2014 | Accent grape berry surface | 20 μm | LA-ESI,MALDI,and ESI-MS | 41 | Amino acids,carbohydrates,and anthocyanins | Location of carbohydrates and anthocyanins in berry surface | [66] |
2014 | Glycyrrhiza glabra L. | 10-30 μm | MALDI | 24 | Flavonoids,flavonoid glycosides,and saponins | Biosynthetic pathway of flavonoids and saponins | [67] |
2015 | Brassica napus | 10 μm | MALDI | 93 | Sinapines,methyl sinapates,cyclic spermidine conjugates,triacylglycerols,and PCs | Translocation of metabolite in matureation and early germination stages | [68] |
2015 | H. perforatum and H. olympicum | 10-15 μm | MALDI | 11 | Naphthodianthrone and flavonoids | Biosynthetic pathway and storage location of hypericin and emodin | [72] |
2016 | Paeonia lactiflora | 10 μm | MALDI | 33 | Amino acids,carbohydrates,lipids,and monoterpenes | Biosynthetic pathway of gallotannins and monoterpene glucosides | [71] |
2017 | Brassica napus | 40 μm | MALDI | 27 | PCs and TAGs | Lipid synthesis in oil seeds | [73] |
2018 | Ginkgo biloba L. | 50 μm | MALDI | 69 | Flavonoids,organic acids,saccharides,phospholipids,chlorophylls,and ginkgolides | Biosynthesis pathways of ginkgo metabolites | [69] |
2018 | Solanum lycopersicum root | 60 μm | MALDI | 35 | Peptides,proteins,and secondary metabolites | Location of secondary metabolites,peptides,and proteins in plant tissues | [78] |
2019 | Emiliania huxleyi | 100 μm | MALDI | 24 | Chlorophyll,vGSLs,BLL,DGCC,PDPT,and PC | Host-virus interactions and their metabolic landscape | [77] |
2020 | Solanum lycopersicum root | 50 μm | MALDI | 9 | Acylsucrose,steroidal glycoalkaloids,lignans,hydroxycinnamic acids,and organic acids | Location of systemically induced root exudation of metabolites(SIREM) | [76] |
2020 | Solanum lycopersicum | 65 μm | MALDI | 23 | Steroidal glycoalkaloids(e.g.,α-tomatine,(dehydro-)α-tomatine,and dehydrotomatine)and anthocyanins | Trace the steroidal glycoalkaloids pathway in tomato fruit for gene function verification | [75] |
2020 | Camellia sinensis | 1.7 mm | LC-MS/MS | 56 | Catechins,alkaloids,theanine,theaflavins,flavone,amino acids,and phenolic acids | Metabolite changes of tea plant response to the wounding | [70] |
Single-Cell Imaging | |||||||
2012 | HeLa cells | 7 μm | MALDI | 22 | DIOC6 and phospholipids | Location of DIOC6 and phospholipids within a single cell | [86] |
2016 | Catharanthus Roseus cells | 20 μm | MALDI and Live single-cell MS | 12 | TIA including catharanthine,ajmalicine,and strictosidine | Synthetic pathway and accumulation location of TIA | [16] |
2017 | P. caudatum and Rotifera cells | 1.4 μm | MALDI | 19 | DAGs,PCs,phosphatidylserines,monoglycerides,ceramides,and small peptides | Subcellular imaging of lipid,metabolite,and peptide within a single cell | [87] |
2019 | HeLa cells | 250 nm | NDPI | 6 | Proflavine and its metabolites,methylthioninium chloride | Subcellular imaging of proflavine and its metabolites within a single cell | [88] |
2020 | HeLa cells | 250 nm | NDPI | 3 | Proflavine,ethacridine,and potential metabolites | Spatial differentiation of proflavine and ethacridine within a single cell | [89] |
2020 | HeLa cells | 250 nm | NDPI | 10 | AgNPs and AuNPs | Location of AuNPs and AgNPs within a single cell | [90] |
2020 | HeLa cells | 300 nm | NLP-based LDI | 6 | Acriflavine,azure B,folate acid,daunorubicin,SPIONs | Dynamic process of anticancer drug molecules release from nanoparticle carriers in lysosomes and entering the nucleus finally leading to apoptosis of cancer cells | [91] |
2020 | HeLa cells | 1 μm | SIMS | 24 | AICAR,phospholipids | De novo purine biosynthesis by purinosome | [92] |
2020 | Epithelial cells,sulfur-oxidizing and methane-oxidizing bacterium | 3 μm | MALDI and FISH microscopy | 2 506 | Carotenoids,phospholipids,TAGs,phosphoethanolamine ceramide,fatty acids | Host-microbe symbioses and their metabolic interactions | [93] |
Year | Species | Lateral resolution | Imaging techniques | Nos. of metabolites | Imaging analytes | Involved pathway | Ref. |
---|---|---|---|---|---|---|---|
Animal Tissue Imaging | |||||||
2019 | Prostate cancer tissue | 150 μm | DESI | 25 | Phospholipids,fatty acids,and organic acids | Fatty acid and lipid biosynthesis | [64] |
2019 | Whole-body rat tissue sections | 500 μm | AFADESI | 17 | Epimeric drugs,neurotransmitters(GABA,glutamic acid,and glutamine) | Metabolic pathway of drugs | [65] |
2019 | Esophageal squamous cell carcinoma tissue | 200 μm | AFADESI | 27 | Amino acids,pyrimidines,fatty acids,saccharides,phospholipids,and organic acids | Proline/fatty acid/ polyamine biosynthesis,and glutamine/uridine/ histidine metabolism | [15] |
2020 | Breast cancer tissue | 100 μm | MALDI | 24 | Carnitines and long-chain acylcarnitines | Carnitine system-mediated fatty acid β-oxidation pathway | [62] |
2020 | Rat kidney tissue | 200 μm | AFADESI | 38 | Aristolochic acid I,amino acids,lipids,inosine,adenosine triphosphate,and carnitine | Arginine-creatinine metabolic pathway,urea cycle,and serine biosynthesis | [64] |
Plant Tissue Imaging | |||||||
2008 | Arabidopsis thaliana leaves | 200 μm | MALDI | 3 | Glucosinolates | Location of glucosinolates within a leaf regarding plant defenses | [79] |
2012 | Gossypium hirsutum seed | 50 μm | MALDI | 69 | TAGs,PAs,PEs,PCs,β-sitosterol,and polyphenolic gossypol | Location of TAGs and PCs in cotton embryos | [13] |
2014 | Accent grape berry surface | 20 μm | LA-ESI,MALDI,and ESI-MS | 41 | Amino acids,carbohydrates,and anthocyanins | Location of carbohydrates and anthocyanins in berry surface | [66] |
2014 | Glycyrrhiza glabra L. | 10-30 μm | MALDI | 24 | Flavonoids,flavonoid glycosides,and saponins | Biosynthetic pathway of flavonoids and saponins | [67] |
2015 | Brassica napus | 10 μm | MALDI | 93 | Sinapines,methyl sinapates,cyclic spermidine conjugates,triacylglycerols,and PCs | Translocation of metabolite in matureation and early germination stages | [68] |
2015 | H. perforatum and H. olympicum | 10-15 μm | MALDI | 11 | Naphthodianthrone and flavonoids | Biosynthetic pathway and storage location of hypericin and emodin | [72] |
2016 | Paeonia lactiflora | 10 μm | MALDI | 33 | Amino acids,carbohydrates,lipids,and monoterpenes | Biosynthetic pathway of gallotannins and monoterpene glucosides | [71] |
2017 | Brassica napus | 40 μm | MALDI | 27 | PCs and TAGs | Lipid synthesis in oil seeds | [73] |
2018 | Ginkgo biloba L. | 50 μm | MALDI | 69 | Flavonoids,organic acids,saccharides,phospholipids,chlorophylls,and ginkgolides | Biosynthesis pathways of ginkgo metabolites | [69] |
2018 | Solanum lycopersicum root | 60 μm | MALDI | 35 | Peptides,proteins,and secondary metabolites | Location of secondary metabolites,peptides,and proteins in plant tissues | [78] |
2019 | Emiliania huxleyi | 100 μm | MALDI | 24 | Chlorophyll,vGSLs,BLL,DGCC,PDPT,and PC | Host-virus interactions and their metabolic landscape | [77] |
2020 | Solanum lycopersicum root | 50 μm | MALDI | 9 | Acylsucrose,steroidal glycoalkaloids,lignans,hydroxycinnamic acids,and organic acids | Location of systemically induced root exudation of metabolites(SIREM) | [76] |
2020 | Solanum lycopersicum | 65 μm | MALDI | 23 | Steroidal glycoalkaloids(e.g.,α-tomatine,(dehydro-)α-tomatine,and dehydrotomatine)and anthocyanins | Trace the steroidal glycoalkaloids pathway in tomato fruit for gene function verification | [75] |
2020 | Camellia sinensis | 1.7 mm | LC-MS/MS | 56 | Catechins,alkaloids,theanine,theaflavins,flavone,amino acids,and phenolic acids | Metabolite changes of tea plant response to the wounding | [70] |
Single-Cell Imaging | |||||||
2012 | HeLa cells | 7 μm | MALDI | 22 | DIOC6 and phospholipids | Location of DIOC6 and phospholipids within a single cell | [86] |
2016 | Catharanthus Roseus cells | 20 μm | MALDI and Live single-cell MS | 12 | TIA including catharanthine,ajmalicine,and strictosidine | Synthetic pathway and accumulation location of TIA | [16] |
2017 | P. caudatum and Rotifera cells | 1.4 μm | MALDI | 19 | DAGs,PCs,phosphatidylserines,monoglycerides,ceramides,and small peptides | Subcellular imaging of lipid,metabolite,and peptide within a single cell | [87] |
2019 | HeLa cells | 250 nm | NDPI | 6 | Proflavine and its metabolites,methylthioninium chloride | Subcellular imaging of proflavine and its metabolites within a single cell | [88] |
2020 | HeLa cells | 250 nm | NDPI | 3 | Proflavine,ethacridine,and potential metabolites | Spatial differentiation of proflavine and ethacridine within a single cell | [89] |
2020 | HeLa cells | 250 nm | NDPI | 10 | AgNPs and AuNPs | Location of AuNPs and AgNPs within a single cell | [90] |
2020 | HeLa cells | 300 nm | NLP-based LDI | 6 | Acriflavine,azure B,folate acid,daunorubicin,SPIONs | Dynamic process of anticancer drug molecules release from nanoparticle carriers in lysosomes and entering the nucleus finally leading to apoptosis of cancer cells | [91] |
2020 | HeLa cells | 1 μm | SIMS | 24 | AICAR,phospholipids | De novo purine biosynthesis by purinosome | [92] |
2020 | Epithelial cells,sulfur-oxidizing and methane-oxidizing bacterium | 3 μm | MALDI and FISH microscopy | 2 506 | Carotenoids,phospholipids,TAGs,phosphoethanolamine ceramide,fatty acids | Host-microbe symbioses and their metabolic interactions | [93] |
Ionization technique | Probe | Environment | Lateral resolution | Requirements | LOD | Detected molecular species | |
---|---|---|---|---|---|---|---|
Typical | Optimal | ||||||
Dynamic SIMS | High-energy ion beams | High vacuum | 0.05-1 μm | 30 nm | Slicing,dehydrated,no matrix needed | pmol-fmol | Elements |
Static SIMS | Low-energy ion beams | High vacuum | 0.1-1 μm | 100 nm | Slicing,dehydrated,no matrix needed | pmol-fmol | Elements,metabolite fragments,drug fragments,and lipid fragments |
MALDI | UV laser | High vacuum,low vacuum,or AP | 10-100 μm | 1.7 μm | Slicing,dehydrated,and homogeneous matrix coating | fmol-amol | Metabolites(e.g.,amino acids,alkaloids,glycosides,phenolics,fatty acids,and glycerides),drugs,lipids,peptides,and proteins |
LDI | UV laser | High vacuum,low vacuum,or AP | 10-100 μm | 350 nm | Slicing,dehydrated,no matrix coating | fmol-amol | Metabolites(e.g.,terpenoids,alkaloids,saccharides,glycerides),drugs,and lipids |
DESI | Charged spray | AP | ~ 200 μm | 12 μm | No particular sample preparation needed,tissue imprinting if necessary | fmol | Metabolites(e.g.,amino acids,terpenoids,alkaloids,glycosides,and glycerides),drugs,lipids,and small peptides |
LA-ESI | IR laser and charged spray | AP | 200-300 μm | 30 μm | No particular sample preparation needed but require water content in sample | pmol-fmol | Metabolites(e.g.,amino acids,alkaloids,glycosides,and glycerides),drugs,and lipids,and small peptides |
Ionization technique | Probe | Environment | Lateral resolution | Requirements | LOD | Detected molecular species | |
---|---|---|---|---|---|---|---|
Typical | Optimal | ||||||
Dynamic SIMS | High-energy ion beams | High vacuum | 0.05-1 μm | 30 nm | Slicing,dehydrated,no matrix needed | pmol-fmol | Elements |
Static SIMS | Low-energy ion beams | High vacuum | 0.1-1 μm | 100 nm | Slicing,dehydrated,no matrix needed | pmol-fmol | Elements,metabolite fragments,drug fragments,and lipid fragments |
MALDI | UV laser | High vacuum,low vacuum,or AP | 10-100 μm | 1.7 μm | Slicing,dehydrated,and homogeneous matrix coating | fmol-amol | Metabolites(e.g.,amino acids,alkaloids,glycosides,phenolics,fatty acids,and glycerides),drugs,lipids,peptides,and proteins |
LDI | UV laser | High vacuum,low vacuum,or AP | 10-100 μm | 350 nm | Slicing,dehydrated,no matrix coating | fmol-amol | Metabolites(e.g.,terpenoids,alkaloids,saccharides,glycerides),drugs,and lipids |
DESI | Charged spray | AP | ~ 200 μm | 12 μm | No particular sample preparation needed,tissue imprinting if necessary | fmol | Metabolites(e.g.,amino acids,terpenoids,alkaloids,glycosides,and glycerides),drugs,lipids,and small peptides |
LA-ESI | IR laser and charged spray | AP | 200-300 μm | 30 μm | No particular sample preparation needed but require water content in sample | pmol-fmol | Metabolites(e.g.,amino acids,alkaloids,glycosides,and glycerides),drugs,and lipids,and small peptides |
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