- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Tissue Engineering and Regenerative Medicine
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Phagocytosis and Immune Regulation
- Pluripotent Stem Cells Research
- Neuroendocrine Tumor Research Advances
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Cannabis and Cannabinoid Research
- Immune cells in cancer
- Diet, Metabolism, and Disease
- Adenosine and Purinergic Signaling
- Metabolism, Diabetes, and Cancer
- Cancer Cells and Metastasis
- Neonatal Respiratory Health Research
German Center for Diabetes Research
2017-2024
Heinrich Heine University Düsseldorf
2017-2024
Deutsches Diabetes-Zentrum e.V.
2017-2024
Helmholtz Zentrum München
2017-2024
Technical University of Munich
2017-2019
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...
Abstract Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer factors. However, critical properties PTFs are still poorly understood, such as how these selectively cell type-specific under which conditions they initiate remodelling. Here we show that early endoderm the paradigm PTF Foxa2 epigenetically primed by low levels active modifications in embryonic stem cells (ESC). Priming is...
It is generally accepted that epiblast cells ingress into the primitive streak by epithelial-to-mesenchymal transition (EMT) to give rise mesoderm; however, it less clear how endoderm acquires an epithelial fate. Here, we used embryonic stem cell and mouse embryo knock-in reporter systems combine time-resolved lineage labelling with high-resolution single-cell transcriptomics. This allowed us resolve morphogenetic programs segregate mesoderm from germ layer. Strikingly, while formed...
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...
During pancreas development endocrine cells leave the ductal epithelium to form islets of Langerhans, but morphogenetic mechanisms are incompletely understood. Here, we identify Ca
<title>Abstract</title> Human pancreas development remains incompletely understood due to limited sample access constrained by ethical and practical considerations. Here we investigate whether pigs resemble humans in more closely than rodents, as such, offer a valuable alternative large-animal model. As pig organogenesis is unexplored, first annotated developmental hallmarks lineage markers of differentiation morphogenesis throughout the 114-day gestation. Building on this detailed roadmap,...
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.
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...
Abstract Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer factors. However, critical properties PTFs are still poorly understood, such as how these selectively cell type-specific under which conditions they initiate remodelling. Here we show that early endoderm the paradigm PTF Foxa2 epigenetically primed by low levels active modifications in embryonic stem cells (ESC). Priming is...
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...