A5070392507- Pancreatic function and diabetes
- Diabetes and associated disorders
- Zebrafish Biomedical Research Applications
- Diabetes Management and Research
- Single-cell and spatial transcriptomics
- Pediatric Hepatobiliary Diseases and Treatments
- Viral Infections and Immunology Research
- Neurobiology and Insect Physiology Research
- Developmental Biology and Gene Regulation
- Invertebrate Immune Response Mechanisms
- Liver physiology and pathology
- Hippo pathway signaling and YAP/TAZ
- Physiological and biochemical adaptations
- Congenital heart defects research
- Genetic and Kidney Cyst Diseases
- Celiac Disease Research and Management
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Phagocytosis and Immune Regulation
- Pediatric Urology and Nephrology Studies
- Adipose Tissue and Metabolism
- MicroRNA in disease regulation
- Pancreatitis Pathology and Treatment
- Renal and related cancers
- Metabolism, Diabetes, and Cancer
- Multimodal Machine Learning Applications
TU Dresden
2014-2025
German Center for Diabetes Research
2014-2025
Heinrich Heine University Düsseldorf
2014-2025
Deutsches Diabetes-Zentrum e.V.
2014-2025
Paul Langerhans Institute Dresden
2015-2025
University Hospital Carl Gustav Carus
2018-2025
University of California, San Francisco
2012-2022
Helmholtz Zentrum München
2017-2022
Max Planck Institute for Heart and Lung Research
2013-2017
Consejo Superior de Investigaciones Científicas
2006-2010
Genetic studies have implicated Notch signaling in the maintenance of pancreatic progenitors. However, how regulates quiescent, proliferative or differentiation behaviors progenitors at single-cell level remains unclear. Here, using genetic analyses and a new transgenic system that allows dynamic assessment signaling, we address discrete levels regulate behavior endocrine zebrafish intrapancreatic duct. We find these experience different which turn distinct cellular outcomes. High induce...
The pancreaticobiliary ductal system connects the liver and pancreas to intestine. It is composed of hepatopancreatic (HPD) as well intrahepatic biliary ducts intrapancreatic ducts. Despite its physiological importance, development remains poorly understood. SRY-related transcription factor SOX9 expressed in mammalian system, but perinatal lethality Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned zebrafish assess role development. first show that sox9b...
The fusion of epithelial sheets is an essential morphogenetic event. Here, we study the development abdomen Drosophila as a model bounded epithelia expansion and uncover complex multistep process for generation adult epidermis from histoblasts, founder cells that replace larval during metamorphosis. We find histoblasts experience biphasic cell cycle emit apical projections direct their invasive planar intercalation in between cells. Coordinately, extrude by constriction actomyosin ring...
Inducing beta-cell mass expansion in diabetic patients with the aim to restore glucose homeostasis is a promising therapeutic strategy. Although several vitro studies have been carried out identify modulators of expansion, restoring endogenous vivo has yet be achieved. To potential stimulators replication vivo, we established transgenic zebrafish lines that monitor and allow quantification cell proliferation by using fluorescent ubiquitylation-based cycle indicator (FUCCI) technology. Using...
The proliferative and functional heterogeneity among seemingly uniform cells is a universal phenomenon. Identifying the underlying factors requires single-cell analysis of function proliferation. Here we show that pancreatic beta-cells in zebrafish exhibit different growth-promoting properties, which part reflect differences time elapsed since birth cells. Calcium imaging shows embryonic islet become during early development. At later stages, younger join following differentiation from...
ABSTRACT Regeneration-competent species possess the ability to reverse progression of severe diseases by restoring function damaged tissue. However, cellular dynamics underlying this capability remain unexplored. Here, we have used single-cell transcriptomics map de novo β-cell regeneration during induction and recovery from diabetes in zebrafish. We show that zebrafish has evolved two distinct types somatostatin-producing δ-cells, which term δ1- δ2-cells. Moreover, characterize a small...
The pancreatic beta-cells control glucose homeostasis by secreting insulin in response to nutrient intake. number of is under tight metabolic control, as this increases with higher However, the signaling pathways matching nutrition beta-cell mass plasticity remain poorly defined. By applying pharmacological and genetic manipulations, we show that reactive oxygen species (ROS) regulate dose-dependently proliferation vivo vitro. In particular, reducing ROS levels blocks their nutrients. Using...
Coordination of cellular activity through Ca
Regulation of cell proliferation has been extensively studied in cultured systems that are characterized by coordinated growth and cell-cycle progression relatively uniform size distribution. During the development multicellular organisms, however, division can be temporally uncoupled, signaling pathways regulate these programs poorly understood. A good model for analyzing control such is morphogenesis Drosophila adult abdominal epidermis histoblasts. These cells undergo a series regulated...
Upon mild liver injury, new hepatocytes originate from preexisting hepatocytes. However, if hepatocyte proliferation is impaired, a manifestation of severe biliary epithelial cells (BECs) contribute to through BEC dedifferentiation into progenitor (LPCs), also termed oval or hepatoblast-like (HB-LCs), and subsequent differentiation Despite the identification several factors regulating activation, little known about involved in regulation LPC during regeneration. Using zebrafish model...
Abstract Diabetes is a multifactorial disorder characterized by loss or dysfunction of pancreatic β-cells. β-cells are heterogeneous, exhibiting different glucose sensing, insulin secretion and gene expression. They communicate with other endocrine cell types via paracrine signals between gap junctions. Here, we identify the importance signaling extracellular signal WNT4. We show heterogeneity in Wnt4 expression, most strikingly postnatal maturation period, -positive cells, being more mature...
Abstract While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset juvenile zebrafish, which regulates mass. Histologically, this is underestimated due to phagocytosis by resident macrophages. To investigate apoptosis at molecular level, implement conditional linked Ca 2+ overload....
Islet inflammation and cytokine production are implicated in pancreatic β-cell dysfunction diabetes pathogenesis. However, we lack therapeutics to protect the insulin-producing β-cells from inflammatory damage. Closing this clinical gap requires establishment of new disease models islet facilitate screening efforts aimed at identifying protective agents. Here, have developed a genetic model Interleukin-1β (Il-1β)-driven zebrafish, vertebrate that allows for non-invasive imaging vivo drug...
The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that islets exhibit signs chronic inflammation. These include recruitment tnfα-expressing macrophages activation NF-kB signaling in beta-cells. Using transgenic reporter, activity undetectable juvenile whereas cells...
Malformations of the intrahepatic biliary structure cause cholestasis, a liver pathology that corresponds to poor bile flow, which leads inflammation, fibrosis, and cirrhosis. Although specification epithelial cells (BECs) line ducts is fairly well understood, molecular mechanisms underlying morphogenesis remain largely unknown. Wnt/β‐catenin signaling plays multiple roles in biology; however, its role remains unclear. Using pharmacological genetic tools allow one manipulate signaling, we...
Age-associated deterioration of cellular physiology leads to pathological conditions. The ability detect premature aging could provide a window for preventive therapies against age-related diseases. However, the techniques determining age are limited, as they rely on limited set histological markers and lack predictive power. Here, we implement GERAS (GEnetic Reference Age Single-cell), machine learning based framework capable assigning individual cells chronological stages their...