Biology subjects

Vandenbempt, V.

Publications and source records attributed to Vandenbempt, V..

5 recordsLinked to original sources

bioRxiv2026

PTPRF is a stress responsive cytoskeletal checkpoint that coordinates metabolic adaptation in hepatocytes and β cells

Cytoskeletal remodeling is essential for adaptation to nutrient availability, yet how cells coordinate actin dynamics with glucose homeostasis in metabolic organs remains unclear. Here, we identify a pathway linking metabolic stress to actin reorganization in hepatocytes and pancreatic {beta} cells. This mechanism involves transcriptional repression of the receptor protein tyrosine phosphatase PTPRF by spliced XBP1, a key unfolded protein response factor. In hepatocytes, PTPRF loss under dietary stress enhances insulin signaling, increases mitochondrial respiration and reduces steatosis. Proteomic analyses show that PTPRF interacts with regulators of actin polymerization and cell junctions, and its deletion promotes actin filament organization, shifting metabolism toward oxidative pathways. In {beta} cells, PTPRF deficiency similarly enhances actin polymerization and augments glucose-stimulated insulin secretion in obesity. Collectively, these findings place PTPRF as a nutrient-responsive regulator of cytoskeletal remodeling that coordinates hepatic metabolism and {beta}-cell function, highlighting its potential as a therapeutic target for improving systemic glucose control.

physiology↗

bioRxiv2026

The Human Pancreas Cell Atlas defines a healthy reference framework for disease contextualization and translational benchmarking

A central challenge in single-cell biology is distinguishing disease-associated remodeling from normal cellular heterogeneity. Addressing this challenge requires healthy reference frameworks that capture cellular diversity across individuals, technologies, and biological contexts. Here we present the Human Pancreas Cell Atlas (HPCA), a reference atlas of the healthy human pancreas integrating 815,126 single-cell and single-nucleus transcriptomes from 109 donors across 12 studies, diverse technologies, and demographics. Using benchmarked integration and community-driven annotations, HPCA defines 94 cell types and transcriptional states spanning endocrine, exocrine, immune, and stromal compartments. The atlas identifies rare endocrine populations, including a putative, spatially supported polyhormonal alpha-beta-delta state, and provides a unified framework for interpreting pancreatic cellular variation across diverse biological and demographic covariates. Projection of disease and model-system datasets onto HPCA contextualized endocrine and epithelial remodeling relative to healthy pancreatic states. Diabetes-associated endocrine cells remained embedded within the healthy endocrine state space while exhibiting disease-specific changes, as supported by spatial and eQTL concordance analyses. Integration with a pancreatic ductal adenocarcinoma atlas resolved injury-associated and malignant epithelial ecosystem regions across donors. Finally, the HPCA enables quantitative benchmarking of murine diabetes models and stem-cell-derived islets against human pancreatic reference states. Together, the HPCA establishes a healthy transcriptional coordinate system for interpreting disease-associated pathophysiology, experimental perturbation, and regenerative fidelity, illustrating how reference atlases can function as analytical frameworks rather than static cell catalogs.

bioinformatics↗

bioRxiv2025

Latent plasticity of the human pancreas across development, health, and disease.

The pancreas plays a central role in major human diseases, yet our understanding of its cellular diversity and plasticity remains incomplete. Here, we present a single-cell multiomics atlas of the human pancreas, profiling over four million cells and nuclei from 57 donors across fetal development, adult homeostasis, and type 2 diabetes (T2D). Integrating sc/snRNA-seq, snATAC-seq, VASA-seq, spatial transcriptomics (Xenium), and multiplexed proteomics (CODEX), we resolve gene expression, chromatin accessibility, and spatial organization at high resolution. We identify transcriptionally plastic centroacinar-like cells (pCACs) in adults with fetal-like features, delineate endocrine and exocrine lineage trajectories during development, and uncover HNF1A-defined beta cell epigenetic states. In T2D, we observe shifts in beta cell subtypes and altered regulatory programs. Glucose perturbation of healthy islets reveals cell-type-specific adaptation and stress responses. This atlas provides a foundational framework to understand pancreas biology and the role of cellular plasticity in regeneration and disease.

genomics↗

bioRxiv2025

Volumetric imaging and single-cell RNAseq atlases identify cellular mechanisms of human dental pulp response during tooth decay progression

Dental pulp responses to dental decay, the most prevalent chronic disease worldwide, involve remodeling processes similar to those observed in other human pathological conditions. By integrating volumetric imaging and single-cell analysis across different disease stages in human samples, we uncovered the natural history of dental pulp responses to decay. At early stages, we observed an arterialization of the capillary networks and progressive outward remodeling of the larger vessels. Neurogenesis of nerve endings and the reprogramming of perivascular progenitor cells into fibroblasts are also observed, initiating the physiological reparative response of the stroma. Pathological angiogenesis and nerve regression combined with dental pulp fibrosis at later stages of tooth decay determine irreversible pulpitis. These results provide a basis for understanding dental tissue response to injury, driving a paradigm shift in patient management. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/653296v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@15d1d86org.highwire.dtl.DTLVardef@3d556corg.highwire.dtl.DTLVardef@b33e32org.highwire.dtl.DTLVardef@1b84a1a_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2023

Protein tyrosine phosphatase receptor kappa regulates glycolysis and de novo lipogenesis to promote hepatocyte metabolic reprogramming in obesity

Fat accumulation, de novo lipogenesis, and glycolysis are key drivers of hepatocyte reprogramming and the consequent metabolic dysfunction-associated steatotic liver disease (MASLD). Here we report that obesity leads to dysregulated expression of hepatic protein-tyrosine phosphatases (PTPs). PTPRK was found to be increased in steatotic hepatocytes in both humans and mice, and positively correlated with PPAR{gamma}-induced lipogenic signalling. High-fat-fed PTPRK knockout mice displayed reduced weight gain and hepatic fat accumulation. Phosphoproteomic analysis in primary hepatocytes and hepatic metabolomics identified fructose-1,6-bisphosphatase 1 and glycolysis as PTPRK targets in metabolic reprogramming. Silencing PTPRK in hepatoma cell lines resulted in reduced colony-forming ability and PTPRK knockout mice developed smaller tumours after diethylnitrosamine-induced hepatocarcinogenesis. Our study defines a novel role for PTPRK in regulating hepatic glycolysis, lipid metabolism, and tumour development. PTPRK inhibition may provide therapeutic possibilities in obesity-associated liver diseases. HighlightsO_LIHepatic receptor-type PTPs are increased in MASLD C_LIO_LIPTPRK is expressed in hepatocytes and upregulated in obesity C_LIO_LIPTPRK deficiency reduces body fat mass and liver steatosis in diet-induced obesity C_LIO_LIPTPRK regulates hepatic glycolysis and lipogenesis, promoting tumorigenesis C_LI

cancer biology↗