A5089237406- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Single-cell and spatial transcriptomics
- Metabolism, Diabetes, and Cancer
- Extracellular vesicles in disease
- Diabetes Treatment and Management
- Water resources management and optimization
- Advanced Glycation End Products research
- RNA Research and Splicing
- Cellular transport and secretion
- Diet, Metabolism, and Disease
- Regulation of Appetite and Obesity
- Neuroinflammation and Neurodegeneration Mechanisms
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Receptor Mechanisms and Signaling
- Adipose Tissue and Metabolism
- Water-Energy-Food Nexus Studies
- Lipid Membrane Structure and Behavior
- Congenital heart defects research
- Peroxisome Proliferator-Activated Receptors
- Phagocytosis and Immune Regulation
German Center for Diabetes Research
2017-2025
Heinrich Heine University Düsseldorf
2017-2025
Deutsches Diabetes-Zentrum e.V.
2017-2025
Helmholtz Zentrum München
2015-2024
Technical University of Munich
2017
University of Tehran
2007-2015
University of Göttingen
2013-2015
Max Planck Institute of Experimental Medicine
2010-2015
Max Planck Society
2011
Max Planck Research Unit for Neurogenetics
2010
Oligodendrocytes secrete vesicles into the extracellular space, where they might play a role in neuron-glia communication. These exosomes are small with diameter of 50-100 nm that formed within multivesicular bodies and released after fusion plasma membrane. The intracellular pathways generate poorly defined. Because Rab family guanosine triphosphatases (GTPases) together their regulators important membrane trafficking organizers, we investigated which GTPase-activating proteins interfere...
The transfer of antigens from oligodendrocytes to immune cells has been implicated in the pathogenesis autoimmune diseases. Here, we show that secrete small membrane vesicles called exosomes, which are specifically and efficiently taken up by microglia both vitro vivo. Internalisation exosomes occurs a macropinocytotic mechanism without inducing concomitant inflammatory response. After stimulation with interferon-γ, observe an upregulation MHC class II subpopulation microglia. However,...
Abstract Computational trajectory inference enables the reconstruction of cell state dynamics from single-cell RNA sequencing experiments. However, requires that direction a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank ( https://cellrank.org ) for fate mapping diverse scenarios, including regeneration, reprogramming and disease, which unknown. Our approach combines robustness with directional...
ABSTRACT Deciphering mechanisms of endocrine cell induction, specification and lineage allocation in vivo will provide valuable insights into how the islets Langerhans are generated. Currently, it is ill defined progenitors segregate different subtypes during development. Here, we generated a novel neurogenin 3 (Ngn3)-Venus fusion (NVF) reporter mouse line, that closely mirrors transient endogenous Ngn3 protein expression. To define an roadmap endocrinogenesis, performed single RNA...
Uncertainty exists as to whether the glucose-dependent insulinotropic polypeptide receptor (GIPR) should be activated or inhibited for treatment of obesity. Gipr was recently demonstrated in hypothalamic feeding centers, but physiological relevance CNS remains unknown. Here we show that HFD-fed CNS-Gipr KO mice and humanized (h)GIPR knockin with CNS-hGIPR deletion decreased body weight improved glucose metabolism. In DIO mice, acute central peripheral administration acyl-GIP increases cFos...
Abstract Single-cell genomics technologies enable multimodal profiling of millions cells across temporal and spatial dimensions. Experimental limitations prevent the measurement all-encompassing cellular states in their native dynamics or tissue niche. Optimal transport theory has emerged as a powerful tool to overcome such constraints, enabling recovery original context. However, most algorithmic implementations currently available have not kept up pace with increasing dataset complexity,...
Abstract Single-cell genomic technologies enable the multimodal profiling of millions cells across temporal and spatial dimensions. However, experimental limitations hinder comprehensive measurement under native dynamics in their tissue niche. Optimal transport has emerged as a powerful tool to address these constraints facilitated recovery original cellular context 1–4 . Yet, most optimal applications are unable incorporate information or scale single-cell atlases. Here we introduce...
Myelin formation is a multistep process that controlled by number of different extracellular factors. During the development central nervous system (CNS), oligodendrocyte progenitor cells differentiate into mature oligodendrocytes start to enwrap axons with myelin membrane sheaths after receiving appropriate signal(s) from axon or its microenvironment. The signals required initiate this are unknown. Here, we show secrete small vesicles, exosome-like space inhibit both morphological...
Homozygous loss-of-function mutations in the gene coding for homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous can cause Maturity-Onset Diabetes of Young 4 (MODY4). Although function Pdx1 is well studied pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas by regulating a downstream transcriptional program. Also, comparative studies binding patterns progenitors adult...
Abstract Transcriptionally mature and immature β-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that subtle differences in β-cell maturity, defined using PDX1 MAFA expression, contribute islet operation. Functional mapping of rodent human islets containing proportionally more HIGH reveals defects metabolism, ionic fluxes secretion. At transcriptomic level, presence increased numbers leads dysregulation gene...
Although multiple pancreatic islet single-cell RNA-sequencing (scRNA-seq) datasets have been generated, a consensus on cell states in development, homeostasis and diabetes as well the value of preclinical animal models is missing. Here, we present an scRNA-seq cross-condition mouse atlas (MIA), curated resource for interactive exploration computational querying. We integrate over 300,000 cells from nine consisting 56 samples, varying age, sex models, including autoimmune type 1 model (NOD),...
Abstract The development of single-molecule co-agonists for the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide (GIP) (GIPR) is considered a breakthrough in treatment obesity type 2 diabetes. But although GIPR–GLP-1R co-agonism decreases body weight with superior efficacy relative to GLP-1R agonism alone preclinical 1–3 clinical studies 4,5 , role GIP regulating energy metabolism remains enigmatic. Increasing evidence suggests that...
The transcription factors (TF) Foxa2 and Pdx1 are key regulators of beta-cell (β-cell) development function. Mutations these TFs or their respective cis-regulatory consensus binding sites have been linked to maturity diabetes the young (MODY), pancreas agenesis, susceptibility in human. Although has shown directly regulate expression during mouse embryonic development, impact this gene regulatory interaction on postnatal β-cell maturation remains obscure. In order easily monitor domains...
Hundreds of missense mutations in the coding region PDX1 exist; however, if these predispose to diabetes mellitus is unknown.
During the development of central nervous system (CNS), oligodendrocytes wrap their plasma membrane around axons to form a multilayered stack tightly attached membranes. Although intracellular myelin compaction and role basic protein has been investigated, forces that mediate close interaction membranes at external surfaces are poorly understood. Such extensive bilayer–bilayer interactions usually prevented by repulsive generated glycocalyx, dense confluent layer large negatively charged...
Islets of Langerhans contain heterogeneous populations insulin-producing β-cells. Surface markers and respective antibodies for isolation, tracking, analysis are urgently needed to study β-cell heterogeneity explore the mechanisms harness regenerative potential immature We performed single-cell mRNA profiling early postnatal mouse islets re-analyzed several sequencing datasets from human pancreas islets. used primary islets, iPSC-derived endocrine cells, Min6 insulinoma, EndoC-βH1 lines FAC...