Analyzing cell-type-specific dynamics of metabolism in kidney repair.

Autor: Wang G; Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands.; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands., Heijs B; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands.; Center of Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands., Kostidis S; Center of Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands., Mahfouz A; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.; Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands.; Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands., Rietjens RGJ; Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands., Bijkerk R; Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands., Koudijs A; Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands., van der Pluijm LAK; Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands., van den Berg CW; Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands.; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands., Dumas SJ; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven and Center for Cancer Biology, VIB, Leuven, Belgium., Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven and Center for Cancer Biology, VIB, Leuven, Belgium.; Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus, Denmark., Giera M; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands.; Center of Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands., van den Berg BM; Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands., Rabelink TJ; Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands. a.j.rabelink@lumc.nl.; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands. a.j.rabelink@lumc.nl.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2022 Sep; Vol. 4 (9), pp. 1109-1118. Date of Electronic Publication: 2022 Aug 25.
DOI: 10.1038/s42255-022-00615-8
Abstrakt: A common drawback of metabolic analyses of complex biological samples is the inability to consider cell-to-cell heterogeneity in the context of an organ or tissue. To overcome this limitation, we present an 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 of cell-type-specific dynamic changes in central carbon metabolism in the context of a complex heterogeneous tissue architecture, such as the kidney. Combined with multiplexed immunofluorescence staining, this method can detect metabolic changes and nutrient partitioning in targeted cell types, as demonstrated in a bilateral renal ischemia-reperfusion injury (bIRI) experimental model. Our approach enables us to identify region-specific metabolic perturbations associated with the lesion and throughout recovery, including unexpected metabolic anomalies in cells with an apparently normal phenotype in the recovery phase. These findings may be relevant to an understanding of the homeostatic capacity of the kidney microenvironment. In sum, this method allows us to achieve resolution at the single-cell level in situ and hence to interpret cell-type-specific metabolic dynamics in the context of structure and metabolism of neighboring cells.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: