Small molecule metabolites: discovery of biomarkers and therapeutic targets

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

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Regulation of membrane protein structure and function by their lipid nano-environment

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(2), P. 107 - 122

Published: Sept. 2, 2022

Language: Английский

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Sphingolipids control dermal fibroblast heterogeneity

Science, Journal Year: 2022, Volume and Issue: 376(6590)

Published: April 14, 2022

Human cells produce thousands of lipids that change during cell differentiation and can vary across individual the same type. However, we are only starting to characterize function these cell-to-cell differences in lipid composition. Here, measured lipidomes transcriptomes human dermal fibroblasts by coupling high-resolution mass spectrometry imaging with single-cell transcriptomics. We found variations specific metabolic pathways contribute establishment states involved organization skin architecture. Sphingolipid composition is shown define fibroblast subpopulations, sphingolipid rewiring driving cell-state transitions. Therefore, heterogeneity affects determination states, adding a new regulatory component self-organization multicellular systems.

Language: Английский

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Lipid metabolism around the body clocks

Progress in Lipid Research, Journal Year: 2023, Volume and Issue: 91, P. 101235 - 101235

Published: May 15, 2023

Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations lipid are responsible for the development various pathologies comprising metabolic syndrome, obesity, type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative most cells our body, coordinate temporal homeostasis. In this review we summarize current knowledge on regulation digestion, absorption, transportation, biosynthesis, catabolism, storage. Specifically, focus molecular interactions between functional clockwork biosynthetic pathways major classes cholesterol, fatty acids, triacylglycerols, glycerophospholipids, glycosphingolipids, sphingomyelins. A growing body epidemiological studies associate a socially imposed misalignment common modern society incidence disorders, however disruption rhythms connection has only been recently revealed. Here, highlight recent unravel mechanistic link intracellular clocks, homeostasis diseases based animal models clock innovative translational humans. We also discuss perspectives manipulating oscillators as potentially powerful approach preventing managing disorders human patients.

Language: Английский

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Spatial metabolomics: from a niche field towards a driver of innovation

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

Published: Sept. 7, 2023

Language: Английский

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Mass spectrometry imaging: the rise of spatially resolved single-cell omics

Nature Methods, Journal Year: 2023, Volume and Issue: 20(3), P. 327 - 330

Published: March 1, 2023

Language: Английский

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Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 25, 2023

Single-cell (SC) analysis provides unique insight into individual cell dynamics and cell-to-cell heterogeneity. Here, we utilize trapped ion mobility separation coupled with dual-polarity ionization mass spectrometry imaging (MSI) to enable high-throughput in situ profiling of the SC lipidome. Multimodal imaging, which dual-polarity-mode MSI is used perform serial data acquisition runs on cells, significantly enhanced lipidome coverage. High-spatial resolution SC-MSI identifies both inter- intracellular lipid heterogeneity; this heterogeneity further explicated by Uniform Manifold Approximation Projection machine learning-driven classifications. We characterize alteration response stearoyl-CoA desaturase 1 inhibition and, additionally, identify cell-layer specific distribution patterns mouse cerebellar cortex. This integrated multimodal technology enables high-resolution spatial mapping intercellular heterogeneity, remodeling induced pharmacological intervention, region-specific diversity within tissue.

Language: Английский

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The multimodality cell segmentation challenge: toward universal solutions

Nature Methods, Journal Year: 2024, Volume and Issue: 21(6), P. 1103 - 1113

Published: March 26, 2024

Language: Английский

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Multiscale biochemical mapping of the brain through deep-learning-enhanced high-throughput mass spectrometry

Nature Methods, Journal Year: 2024, Volume and Issue: 21(3), P. 521 - 530

Published: Feb. 16, 2024

Abstract Spatial omics technologies can reveal the molecular intricacy of brain. While mass spectrometry imaging (MSI) provides spatial localization compounds, comprehensive biochemical profiling at a brain-wide scale in three dimensions by MSI with single-cell resolution has not been achieved. We demonstrate complementary and mapping using MEISTER, an integrative experimental computational (MS) framework. Our framework integrates deep-learning-based reconstruction that accelerates high-mass-resolving MS 15-fold, multimodal registration creating three-dimensional (3D) distributions data integration method fitting cell-specific spectra to 3D datasets. imaged detailed lipid profiles tissues millions pixels large populations acquired from rat identified region-specific contents localizations lipids depending on both cell subpopulations anatomical origins cells. workflow establishes blueprint for future development multiscale characterization

Language: Английский

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Establishing a conceptual framework for holistic cell states and state transitions

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2633 - 2651

Published: May 1, 2024

Cell states were traditionally defined by how they looked, where located, and what functions performed. In this post-genomic era, the field is largely focused on a molecular view of cell state. Moving forward, we anticipate that observables used to define will evolve again as single-cell imaging analytics are advancing at breakneck pace via collection large-scale, systematic image datasets application quantitative image-based data science methods. This is, therefore, key moment in arc biological research develop approaches integrate spatiotemporal physical structure organization with toward concept holistic perspective, propose conceptual framework for state transitions data-driven, practical, useful enable integrative analyses modeling across many types.

Language: Английский

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