A5003678897- Pancreatic function and diabetes
- Diabetes and associated disorders
- Metabolism, Diabetes, and Cancer
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Diabetes Treatment and Management
- Phagocytosis and Immune Regulation
- Diabetes Management and Research
- Cellular transport and secretion
- 3D Printing in Biomedical Research
- Gene Regulatory Network Analysis
- Neonatal Respiratory Health Research
- Gene expression and cancer classification
- Plant Stress Responses and Tolerance
- Gaussian Processes and Bayesian Inference
- Adenosine and Purinergic Signaling
- Plant Micronutrient Interactions and Effects
- Neuroendocrine Tumor Research Advances
- Diet, Metabolism, and Disease
- Endoplasmic Reticulum Stress and Disease
- Aluminum toxicity and tolerance in plants and animals
German Center for Diabetes Research
2019-2025
Heinrich Heine University Düsseldorf
2019-2025
Deutsches Diabetes-Zentrum e.V.
2019-2025
Helmholtz Zentrum München
2019-2022
Technical University of Munich
2019-2022
Klinikum rechts der Isar
2021
Universidad Complutense de Madrid
2014
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...
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...
In bread wheat, besides malate, the importance of citrate efflux for Al tolerance has also been reported. For better understanding mechanism in here, we performed both a molecular characterization transporter gene TaMATE1 and an investigation on upstream variations malate genes. belong to multidrug protein family, which are located long arm homoeologous group 4 chromosomes ( TaMATE1‐4A , TaMATE1‐4B TaMATE1‐4D ). homoeologues transcript expression study exhibited preponderance homoeologue...
During pancreas development endocrine cells leave the ductal epithelium to form islets of Langerhans, but morphogenetic mechanisms are incompletely understood. Here, we identify Ca
Translation of basic research from bench-to-bedside relies on a better understanding similarities and differences between mouse human cell biology, tissue formation, organogenesis. Thus, establishing ex vivo modeling systems pancreas development will help not only to understand evolutionary conserved mechanisms differentiation morphogenesis but also pathomechanisms disease design strategies for engineering.
Protein disulfide isomerases (PDIs) are oxidoreductases that involved in catalyzing the formation and rearrangement of bonds during protein folding. One PDI members is PDI-associated 6 (PDIA6) protein, which has been shown to play a vital role β-cell dysfunction diabetes. However, very little known about function this β-cells vivo. This study aimed describe consequences point mutation Pdia6 on development function.We generated an ENU mouse model carrying missense (Phe175Ser) second...
Synaptotagmin-13 (Syt13) is an atypical member of the vesicle trafficking synaptotagmin protein family. The expression pattern and biological function this Ca2+-independent are not well resolved. Here, we have generated a novel Syt13-Venus fusion (Syt13-VF) fluorescence reporter allele to track isolate tissues cells expressing Syt13 protein. regulated by endogenous cis-regulatory elements follows identical homozygous mice viable fertile. We identify Syt13-VF in different regions brain with...
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. We show that HFD-fed CNS-Gipr ko mice and humanized (h)GIPR knock-in with CNS-hGIPR deletion improved body weight glycemia, these metabolic improvements vanish upon adult-onset deletion. In DIO mice, acute central...
Abstract Nkx6-1 is a member of the Nkx family homeodomain transcription factors (TF) that regulates motor neuron development, specification and pancreatic endocrine β-cell differentiation. To facilitate isolation tracking Nkx6-1-expressing cells, we have generated novel Venus Fusion (Nkx6-1-VF) reporter allele. The Nkx6-1-VF knock-in regulated by endogenous cis-regulatory elements fluorescent protein fusion does not interfere with TF function, as homozygous mice are viable fertile. In...
Nkx6-1 is a member of the Nkx family homeodomain transcription factors (TFs) that regulates motor neuron development, specification and pancreatic endocrine β-cell differentiation. To facilitate isolation tracking Nkx6-1-expressing cells, we have generated novel Venus fusion (Nkx6-1-VF) reporter allele. The Nkx6-1-VF knock-in regulated by endogenous cis-regulatory elements fluorescent protein does not interfere with TF function, as homozygous mice are viable fertile. nuclear localization...
Abstract Epithelial cell egression is important for organ development, but also drives cancer metastasis. Better understandings of pancreatic epithelial morphogenetic programs generating islets Langerhans aid to diabetes therapy. Here we identify the Ca 2+ -independent atypical Synaptotagmin 13 (Syt13) as a key driver endocrine and islet formation. We detected upregulation Syt13 in precursors that correlates with increased expression unique cytoskeletal components. High-resolution imaging...
Abstract Synaptotagmin13 (Syt13) is an atypical member of the vesicle trafficking Synaptotagmin protein family. The expression pattern and biological function this Ca 2+ -independent are not well resolved. Here, we have generated a novel Syt13-Venus fusion (Syt13-VF) fluorescence reporter allele to track isolate tissues cells expressing Syt13 protein. regulated by endogenous cis-regulatory elements follows identical homozygous mice viable fertile. We identify Syt13-VF in different regions...
This experimental mouse study examined whether or not dedifferentiated β cells could be reversed targeted by pharmacological intervention for diabetes remission. They identified evidence β-cell dedifferentiation and dysfunction which single combined approaches.