A5040884856- Pancreatic function and diabetes
- Liver physiology and pathology
- Pediatric Hepatobiliary Diseases and Treatments
- Pancreatic and Hepatic Oncology Research
- Renal and related cancers
- Growth Hormone and Insulin-like Growth Factors
- Liver Disease Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Organ Transplantation Techniques and Outcomes
- MicroRNA in disease regulation
- Pancreatitis Pathology and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Genetic and Kidney Cyst Diseases
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Pluripotent Stem Cells Research
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- FOXO transcription factor regulation
- Cancer-related gene regulation
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Protein Kinase Regulation and GTPase Signaling
de Duve Institute
2015-2024
UCLouvain
2014-2024
GTx (United States)
2008-2011
Johns Hopkins Medicine
2005
Johns Hopkins University
2005
Euroscreen (Belgium)
2002
Vanderbilt University
1999
KU Leuven
1987-1999
Karolinska Institutet
1997
University of Massachusetts Amherst
1993
In the mammalian liver, bile is transported to intestine through an intricate network of ducts. Notch signaling required for normal duct formation, but its mode action has been unclear. Here, we show in mice that ducts arise a novel mechanism tubulogenesis involving sequential radial differentiation. activated subset liver progenitor cells fated become ductal cells, and pathway activation necessary biliary fate. signals are also morphogenesis, hepatic lobule promotes ectopic differentiation...
Insulin release from pancreatic beta-cells plays an essential role in blood glucose homeostasis. Several proteins controlling insulin exocytosis have been identified, but the factors determining expression of components secretory machinery remain largely unknown. MicroRNAs are newly discovered small non-coding RNAs acting as repressors gene expression. We found that overexpression mir-9 insulin-secreting cells causes a reduction elicited by or potassium. show acts diminishing transcription...
During liver development, hepatocytes and biliary cells differentiate from common progenitors called hepatoblasts. The factors that control hepatoblast fate decision are unknown. Here we report a gradient of activin/TGFbeta signaling controls differentiation. High is required near the portal vein for differentiation cells. Onecut transcription HNF-6 OC-2 inhibit in parenchyma, this allows normal hepatocyte In absence factors, shape perturbed hepatoblasts into hybrid display characteristics...
In many organs, including the intestine and skin, cancers originate from cells of stem or progenitor compartment. Despite its nomenclature, cellular origin hepatocellular carcinoma (HCC) remains elusive. contrast to most liver lacks a defined cell population for organ maintenance. Previous studies suggest that both hepatocytes facultative within biliary compartment are capable generating HCC. As HCCs with signature carry worse prognosis, understanding HCC is clinical relevance. Here, we used...
During liver development, hepatoblasts differentiate into hepatocytes or biliary epithelial cells (BEC). The BEC delineate the intrahepatic and extrahepatic bile ducts, gallbladder. transcription factors that control development of tract are unknown. Previous work has shown onecut factor HNF6 is expressed in gallbladder primordium. We now show also developing investigate its involvement by analyzing phenotype Hnf6–/– mice. In these mice, was absent, ducts were abnormal perturbed prenatal...
Hepatocyte nuclear factor 6 (HNF-6) is the prototype of a new class cut homeodomain transcription factors. During mouse development, HNF-6 expressed in epithelial cells that are precursors exocrine and endocrine pancreatic cells. We have investigated role pancreas differentiation by inactivating its gene mouse. In hnf6(-/-) embryos, appeared to be normal but cell was impaired. The expression neurogenin 3 (Ngn-3), essential for determination precursors, almost abolished. Consistent with this,...
<h3>Objective</h3> Growing evidence suggests that a phenotypic switch converting pancreatic acinar cells to duct-like can lead intraepithelial neoplasia and eventually invasive ductal adenocarcinoma. Histologically, the onset of this is characterised by co-expression markers in acini, lesion called acinar-to-ductal metaplasia (ADM). The transcriptional regulators required initiate ADM are unknown, but need be identified characterise regulatory networks drive ADM. In study, role transcription...
During pancreatic organogenesis endocrine cells arise from non self-renewing progenitors that express Ngn3. The precursors give rise to Ngn3+ are presumably located within duct-like structures. However, the nature of such is poorly understood. We show that, at E13-E18, embryonic stage during which major burst beta-cell neogenesis takes place, duct Hnf1beta, product maturity-onset diabetes young type 5 (MODY5) gene. this invariably cluster with mitotically competent Hnf1beta+ cells, and often...
Tissue-specific transcription is regulated in part by cell type-restricted proteins that bind to defined sequences target genes. The DNA-binding domain of these often evolutionarily conserved. On this basis, liver-enriched factors were classified into five families. We describe here the mammalian prototype a sixth family, which we therefore call hepatocyte nuclear factor 6 (HNF-6). It activates promoter gene involved control glucose metabolism. HNF-6 contains two different domains. One...