Large-Scale Metabolite Imaging Gallery of Mouse Organ Tissues to Study Spatial Metabolism DOI
Karl W. Smith, Antonia Fecke,

Siva Swapna Kasarla

et al.

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Mass spectrometry imaging (MSI) has revolutionized the study of tissue metabolism by enabling visualization small molecule metabolites (SMMs) with high spatial resolution. However, comprehensive SMM databases for different organ tissues are lacking, hindering our understanding metabolism. To address this resource gap, we present a large-scale gallery mouse brain, kidney, and liver, capturing SMMs spanning eight chemical super classes encompassing over 40 metabolic pathways. Manual curation display these data sets unveil patterns that less documented in reported organs. Specifically, identify 65 brain coronal sections 71 sagittal sections, including neurotransmitters. Furthermore, map 98 kidneys 66 providing insights into their amino acid glutathione Our insightful serves as critical research community, filling significant gap. This is freely available download can be accessed through BioImage Archive METASPACE repositories, high-quality annotated images potential future computational models advancing at level.

Language: Английский

Small molecule metabolites: discovery of biomarkers and therapeutic targets DOI Creative Commons
Shi Qiu, Ying Cai, Hong Yao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

Citations

388

Analyzing cell-type-specific dynamics of metabolism in kidney repair DOI Creative Commons
Gangqi Wang, Bram Heijs, Sarantos Kostidis

et al.

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(9), P. 1109 - 1118

Published: Aug. 25, 2022

Abstract A common drawback of metabolic analyses complex biological samples is the inability to consider cell-to-cell heterogeneity in context an organ or tissue. To overcome this limitation, we present advanced high-spatial-resolution metabolomics approach using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) combined with isotope tracing. This method allows mapping cell-type-specific dynamic changes central carbon metabolism a heterogeneous tissue architecture, such as kidney. Combined multiplexed immunofluorescence staining, can detect and nutrient partitioning targeted cell types, demonstrated bilateral renal ischemia–reperfusion injury (bIRI) experimental model. Our enables us identify region-specific perturbations associated lesion throughout recovery, including unexpected anomalies cells apparently normal phenotype recovery phase. These findings may be relevant understanding homeostatic capacity kidney microenvironment. In sum, achieve resolution at single-cell level situ hence interpret dynamics structure neighboring cells.

Language: Английский

Citations

119

Physiological and pathological roles of lipogenesis DOI
Yong Geun Jeon, Ye Young Kim, Gung Lee

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(5), P. 735 - 759

Published: May 4, 2023

Language: Английский

Citations

114

Spatial dynamic metabolomics identifies metabolic cell fate trajectories in human kidney differentiation DOI Creative Commons
Gangqi Wang, Bram Heijs, Sarantos Kostidis

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(11), P. 1580 - 1593.e7

Published: Nov. 1, 2022

Accumulating evidence demonstrates important roles for metabolism in cell fate determination. However, it is a challenge to assess at spatial resolution that acknowledges both heterogeneity and cellular dynamics its tissue microenvironment. Using multi-omics platform study cell-type-specific complex tissues, we describe the metabolic trajectories during nephrogenesis developing human kidney. Exploiting situ analysis of isotopic labeling, shift from glycolysis toward fatty acid β-oxidation was observed differentiation renal vesicle S-shaped body proximal tubules. In addition, show hiPSC-derived kidney organoids are characterized by immature phenotype fails use mitochondrial long-chain acids energy metabolism. Furthermore, supplementation butyrate enhances tubular epithelial maturation cultured organoids. Our findings highlight relevance understanding efficiently guide stem differentiation.

Language: Английский

Citations

73

Spatial metabolomics: from a niche field towards a driver of innovation DOI
Theodore Alexandrov

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(9), P. 1443 - 1445

Published: Sept. 7, 2023

Language: Английский

Citations

49

Multiplex protein imaging in tumour biology DOI
Natalie de Souza, Shan Zhao, Bernd Bodenmiller

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(3), P. 171 - 191

Published: Feb. 5, 2024

Language: Английский

Citations

33

Transcriptomic, epigenomic, and spatial metabolomic cell profiling redefines regional human kidney anatomy DOI Creative Commons
Haikuo Li, Dian Li, Nicolas Ledru

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(5), P. 1105 - 1125.e10

Published: March 20, 2024

A large-scale multimodal atlas that includes major kidney regions is lacking. Here, we employed simultaneous high-throughput single-cell ATAC/RNA sequencing (SHARE-seq) and spatially resolved metabolomics to profile 54 human samples from distinct anatomical regions. We generated transcriptomes of 446,267 cells chromatin accessibility profiles 401,875 developed a package analyze 408,218 metabolomes. find the same cell type, including thin limb, thick ascending limb loop Henle principal cells, display transcriptomic, accessibility, metabolomic signatures, depending on anatomic location. Surveying metabolism-associated gene revealed non-overlapping metabolic signatures between nephron segments dysregulated lipid metabolism in diseased proximal tubule (PT) cells. Integrating omics with clinical data identified PLEKHA1 as disease marker, its vitro knockdown increased expression PT differentiation, suggesting possible pathogenic roles. This study highlights previously underrepresented cellular heterogeneity underlying anatomy.

Language: Английский

Citations

33

Spatial multi-omics: novel tools to study the complexity of cardiovascular diseases DOI Creative Commons
Paul Kießling, Christoph Kuppe

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 18, 2024

Abstract Spatial multi-omic studies have emerged as a promising approach to comprehensively analyze cells in tissues, enabling the joint analysis of multiple data modalities like transcriptome, epigenome, proteome, and metabolome parallel or even same tissue section. This review focuses on recent advancements spatial multi-omics technologies, including novel computational approaches. We discuss low-resolution high-resolution methods which can resolve up 10,000 individual molecules at subcellular level. By applying integrating these techniques, researchers recently gained valuable insights into molecular circuits mechanisms govern cell biology along cardiovascular disease spectrum. provide an overview current approaches, with focus integration datasets, highlighting strengths weaknesses various pipelines. These tools play crucial role analyzing interpreting facilitating discovery new findings, enhancing translational research. Despite nontrivial challenges, such need for standardization experimental setups, analysis, improved tools, application holds tremendous potential revolutionizing our understanding human processes identification biomarkers therapeutic targets. Exciting opportunities lie ahead field will likely contribute advancement personalized medicine diseases.

Language: Английский

Citations

25

Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease DOI
Verónica Miguel, Isaac Shaw, Rafael Kramann

et al.

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Language: Английский

Citations

19

High spatial resolution mass spectrometry imaging for spatial metabolomics: Advances, challenges, and future perspectives DOI
Siyuan Ma,

Yixin Leng,

Xiaoping Li

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2022, Volume and Issue: 159, P. 116902 - 116902

Published: Dec. 26, 2022

Language: Английский

Citations

56