Biology subjects

Rietjens, R. G. J.

Publications and source records attributed to Rietjens, R. G. J..

2 recordsLinked to original sources

bioRxiv2025

Spatial metabolomics reveals persistent localized niche-specific metabolic failure in kidneys following ischemia-reperfusion injury

After acute kidney injury (AKI), the persistence of failed repair proximal tubule (FR-PT) cells is postulated to hamper kidney regeneration and increase the risk of chronic kidney disease. This fibrotic shift likely depends on microenvironmental interactions, which remain largely unstudied. To investigate this, we mapped the spatial metabolic architecture of post-ischemic kidneys using an untargeted semi-quantitative spatial metabolomics (qMSI) approach, integrated with high-resolution spatial transcriptomics. Unsupervised neighborhood clustering of qMSI data revealed distinct microenvironments. Lipidome profiles identified diffusely spread areas with persistent injury markers surrounding FR-PT cells. These niches exhibited decreased linoleic acid and elevated succinic acid levels, even in epithelial cells that appeared otherwise healthy. Corresponding transcriptomic profiles confirmed downregulation of oxidative phosphorylation and fatty acid {beta}-oxidation in these regions. Together, these findings point towards niche-specific metabolic failure and persistent mitochondrial dysfunction in areas considered healthy, underscoring the need to prioritize metabolic resuscitation to prevent long-term consequences of AKI.

biochemistry↗

bioRxiv2021

Fragile X syndrome patient-derived neurons developing in the mouse brain show FMR1 -dependent phenotypes

Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, increased percentages of Arc- and Egr1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons pointed to an increase in synaptic activity and synaptic strength as compared to control. This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3D context, and could be used to test new therapeutic compounds correcting neuronal development defects in FXS.

neuroscience↗