A5065096348- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Dietary Effects on Health
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Metabolism, Diabetes, and Cancer
- 3D Printing in Biomedical Research
- Spaceflight effects on biology
- Diet, Metabolism, and Disease
- Circadian rhythm and melatonin
- African Sexualities and LGBTQ+ Issues
- Planarian Biology and Electrostimulation
- Genetic Syndromes and Imprinting
Nestlé (Switzerland)
2018-2023
Inserm
2013-2019
Université de Strasbourg
2013-2019
Institut de génétique et de biologie moléculaire et cellulaire
2014-2019
Centre National pour la Recherche Scientifique et Technique (CNRST)
2019
Centre National de la Recherche Scientifique
2019
École Polytechnique Fédérale de Lausanne
2019
Institut de Biologie Moléculaire et Cellulaire
2012
Increasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show Rfx6, whose mutation leads to neonatal diabetes humans, is essential maintain key features functionally mature cells mice. Rfx6 adult glucose intolerance, impaired sensing, and defective secretion. This associated with reduced expression core components secretion pathway, including glucokinase, Abcc8/SUR1 subunit KATP...
Development and function of pancreatic β cells involve the regulated activity specific transcription factors. RFX6 is a factor essential for mouse cell differentiation that mutated in monogenic forms neonatal diabetes. However, expression functional roles human cells, especially pathophysiological conditions, are poorly explored. We demonstrate presence adult endocrine cells. Using recently developed line EndoC-βH2, we show regulates insulin gene transcription, content, secretion. Knockdown...
Enteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake storage. Our goal is decipher gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context, we studied role transcription factor Rfx6 which had been identified as cause Mitchell–Riley syndrome, characterized by neonatal diabetes congenital malabsorptive diarrhea. We previously reported...
The transcription factor neurogenin3 (Ngn3) triggers islet cell differentiation in the developing pancreas. However, little is known about molecular mechanisms coupling cycle exit and Ngn3+ progenitors. We identified a novel effector of Ngn3 endocrinogenic function, p21 protein–activated kinase Pak3, to control neuronal implicated X-linked intellectual disability humans. show that Pak3 expression initiated endocrine progenitor cells next maintained maturing hormone-expressing during pancreas...
The synchronization of circadian clock depends on a central pacemaker located in the suprachiasmatic nuclei. However, potential feedback peripheral signals remains poorly characterized. To explore whether organ clocks may affect pacemaker, we used chimeric model which mouse hepatocytes were replaced by human hepatocytes. Liver humanization led to reprogrammed diurnal gene expression and advanced phase liver that extended muscle entire rhythmic physiology. Similar clock-deficient mice,...
In type 1 diabetes, a renewable source of human pancreatic β cells, in particular from induced pluripotent stem cell (hiPSC) origin, would greatly benefit therapy. Earlier work showed that progenitors differentiated embryonic cells vitro can further mature to become glucose responsive following macroencapsulation and transplantation mice. Here we took similar approach optimizing the generation hiPSCs. This demonstrates hiPSCs endoderm be efficiently robustly generated under large-scale...
Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration onset are common occurrences the aging population. iPSCs could offer regenerative medical options for age-related elderly. However, reprogramming somatic cells from elderly inefficient when successful at all. Perhaps due to their low rates of replication culture, traditional transduction approaches with centenarian fibroblasts met little success. A simple...
Purpose Great progresses have been made for generating in vitro pluripotent stem cell pancreatic β‐like cells. However, the maturation stage of cells still requires vivo to recreate environmental niche. A deeper understanding factors promoting is great interest clinical applications. Experimental design Label‐free mass spectrometry based proteomic analysis performed on samples from a longitudinal study differentiation human induced toward glucose responsive insulin producing Results Proteome...
ABSTRACT Objective Enteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake storage. Our goal is decipher gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context, we studied role transcription factor Rfx6 which had been identified as cause Mitchell-Riley syndrome characterized by neonatal diabetes congenital malabsorptive diarrhea. We...
ABSTRACT The circadian clock is an evolutionarily acquired gene network that synchronizes physiological processes to adapt homeostasis the succession of day and night. While most mammalian cells have a clock, their synchronization at body-level depends on central pacemaker located in suprachiasmatic nuclei hypothalamus integrates light signals. However, peripheral organs are also synchronized by feeding cues can uncoupled them from pacemaker. Nevertheless, potential feedback signals remains...