Biology subjects

Kardinal, R.

Publications and source records attributed to Kardinal, R..

4 recordsLinked to original sources

bioRxiv2025

Endothelial deletion of ADGRF5 (GPR116) promotes fibro-inflammatory EndMT and impairs adaptive thermogenesis in brown adipose tissue

ObjectiveBrown adipose tissue (BAT) dissipates energy via non-shivering thermogenesis, and it is a promising therapeutic target for metabolic disease. While most research focuses on thermogenic adipocytes, emerging data point to critical contributions from the surrounding stromal niche. Here, we investigated the role of adhesion G protein-coupled receptors (aGPCRs) in BAT function, focusing on Adgrf5 (Gpr116), a receptor enriched in endothelial cells. MethodsWe used single-nuclei RNA sequencing to map aGPCRs expression across mouse and human BAT. We then examined the consequences of Adgrf5(Gpr116) loss using global, brown adipocyte, and endothelial-specific knockout mouse models under acute and prolonged cold exposure. ResultsInducible endothelial deletion of Adgrf5(Gpr116) impaired the maintenance of thermogenic capacity during prolonged--but not acute--cold exposure. This was not associated with defective angiogenesis, but rather with endothelial fibro-inflammatory reprogramming. Single-nuclei RNA sequencing analysis revealed endothelial-to- mesenchymal transition (EndMT) features, including induction of mesenchymal markers, collagens, and metalloproteinases, and loss of barrier genes. Adgrf5(Gpr116)-deficient endothelial cells also exhibited cytoskeletal remodeling and activation of stress fiber pathways, implicating Adgrf5(Gpr116) as a mechanosensory safeguard of endothelial identity. ConclusionEndothelial Adgrf5(Gpr116) preserves thermogenic competence in BAT by suppressing EndMT and maladaptive matrix remodeling. Our findings establish vascular mechanosensing as a critical determinant of thermogenic tissue homeostasis. HighlightsO_LIAdhesion GPCRs are the second most abundant GPCR family in mouse and human brown fat C_LIO_LIAdhesion GPCRs are enriched in non-adipocyte cell types in brown fat and participate in cell-cell contact signaling C_LIO_LIEndothelial Adgrf5(Gpr116) is required for thermogenic adaptation during prolonged cold exposure C_LIO_LILoss of Adgrf5(Gpr116) induces fibro-inflammatory reprogramming and endothelial-to-mesenchymal transition (EndMT) C_LI

molecular biology↗

bioRxiv2025

Shiny-Calorie: A context-aware application for indirect calorimetry data analysis and visualization using R

Indirect calorimetry is a cornerstone technique for metabolic phenotyping of animal models in preclinical research, with well-established experimental protocols and platforms. However, a flexible, extensible, and user-friendly software suite that enables standardized integration of data and metadata from diverse metabolic phenotyping platforms--followed by unified statistical analysis and visualization--remains absent. We present Shiny-Calorie, an open-source interactive web application for transparent data and metadata integration, comprehensive statistical data analysis, and visualization of indirect calorimetry datasets. Shiny-Calorie is compatible with data formats from widely used commercial metabolic phenotyping platforms, such as TSE and Sable Systems, and includes functionality for exporting processed data in these formats. Built using GNU R and a Shiny-based reactive interface, Shiny-Calorie enables intuitive exploration of complex, multi-modal longitudinal datasets comprising categorical, continuous, ordinal, and count variables. The platform incorporates state-of-the-art statistical methods for robust hypothesis testing, thereby facilitating biologically meaningful interpretation of energy metabolism phenotypes, including resting metabolic rate and energy expenditure. Overall, Shiny-Calorie streamlines routine analysis workflows and enhances reproducibility and transparency in metabolic phenotyping studies.

bioinformatics↗

bioRxiv2024

From Planning Stage To FAIR Data: A Practical Metadatasheet For Biomedical Scientists

Datasets consist of measurement data and metadata. Metadata provides context, essential for understanding and (re-)using data. Various metadata standards exist for different methods, systems and contexts. However, relevant information resides at differing stages across the data-lifecycle. Often, this information is defined and standardized only at publication stage, which can lead to data loss and workload increase. In this study, we developed Metadatasheet, a metadata standard based on interviews with members of two biomedical consortia and systematic screening of data repositories. It aligns with the data-lifecycle allowing synchronous metadata recording within Microsoft Excel, a widespread data recording software. Additionally, we provide an implementation, the Metadata Workbook, that offers user-friendly features like automation, dynamic adaption, metadata integrity checks, and export options for various metadata standards. By design and due to its extensive documentation, the proposed metadata standard simplifies recording and structuring of metadata for biomedical scientists, promoting practicality and convenience in data management. This framework can accelerate scientific progress by enhancing collaboration and knowledge transfer throughout the intermediate steps of data creation.

bioinformatics↗

bioRxiv2024

BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue

The primary cilium has emerged as critical in regulating whole-body energy metabolism, as reflected in the Bardet-Biedl syndrome (BBS), where primary cilia dysfunction leads to obesity due to hyperphagia and white adipose tissue (WAT) remodeling. The regulation of cell fate and differentiation of adipocyte precursor cells (APCs) is key to maintaining WAT homeostasis during obesity. Using mice that recapitulated the BBS patient phenotype (Bbs8-/-), we demonstrate that primary cilia dysfunction reduces the stem-cell-like P1 APC subpopulation by inducing a phenotypic switch into a fibrogenic progenitor state, characterized by extracellular matrix (ECM) remodeling and upregulation of CD9. Single-cell RNA sequencing revealed a direct transition of stem-cell-like P1 cells into fibrogenic progenitors, bypassing the committed P2 cells. Ectopic ciliary Hedgehog signaling upon loss of BBS8 emerged as a central driver of the molecular changes in Bbs8-/- APCs, altering differentiation into adipocytes and lipid uptake. These findings unravel a novel role for primary cilia in governing APC fate, determining the delicate balance between adipogenesis and fibrogenesis. The identified molecular mechanisms provide insights into potential therapeutic targets for obesity.

cell biology↗