A5022789546- Single-cell and spatial transcriptomics
- Liver physiology and pathology
- Microbial Natural Products and Biosynthesis
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Plant Disease Resistance and Genetics
- Renal and related cancers
- Carbohydrate Chemistry and Synthesis
- Epigenetics and DNA Methylation
- Extracellular vesicles in disease
- Zebrafish Biomedical Research Applications
- Synthetic Organic Chemistry Methods
- Genomic variations and chromosomal abnormalities
- Genetic and Kidney Cyst Diseases
- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Congenital heart defects research
- Ultrasound and Hyperthermia Applications
- Genomics and Chromatin Dynamics
- Plant Gene Expression Analysis
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Gene expression and cancer classification
Wellcome Sanger Institute
2018-2024
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2016
Centre National de la Recherche Scientifique
2016
Université Paris-Saclay
2016
Institut de Biologie Intégrative de la Cellule
2016
Oxford Fertility
2009
University of Cambridge
2004-2007
NOAA National Ocean Service
2002
Medical University of South Carolina
2002
Universidad de Oviedo
2000-2002
Abstract Recent developments in stem cell biology have enabled the study of fate decisions early human development that are impossible to vivo. However, understanding how varies across individuals and, particular, influence common genetic variants during this process has not been characterised. Here, we exploit iPS lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing population variation endoderm differentiation. We identify molecular markers predictive...
Organoids regenerate human bile ducts Bile carry from the liver and gall bladder to small intestine, where it aids digestion. Cholangiocytes are epithelial cells that line modify as its transported through biliary tree. Chronic diseases involving cholangiocytes account for a large fraction of failure need transplantation. Because donors in short supply, Sampaziotis et al. used organoid technology develop cell-based therapy using tissue (see Perspective by Kurial Willenbring). Cholangiocyte...
Abstract Background Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of embryo from a population haemogenic endothelial which undergo endothelial-to-haematopoietic transition (EHT). Despite progress achieved recent years, molecular mechanisms driving EHT are still poorly understood, especially human where AGM is not easily accessible. Results In this study, we take advantage pluripotent cell (hPSC) differentiation system and...
Heterozygous de novo mutations in GATA6 are the most frequent cause of pancreatic agenesis humans. In mice, however, a similar phenotype requires biallelic loss Gata6 and its paralog Gata4. To elaborate human-specific requirements for GATA6, we chose to model vitro by combining both gene-edited patient-derived pluripotent stem cells (hPSCs) directed differentiation toward β-like cells. We find that heterozygous hPSCs show modest reduction definitive endoderm (DE) formation, while GATA6-null...
Several studies propose an influence of chromatin on pre-mRNA splicing, but it is still unclear how widespread and direct this phenomenon is. We find here that when assembled in vivo, the U2 snRNP co-purifies with a subset chromatin-proteins, including histones remodeling complexes like SWI/SNF. Yet, unbiased RNAi screen revealed outcome splicing influenced by much larger variety factors not all associating spliceosome. The availability broad range impacting further unveiled their very...
Mithramycin is an aureolic acid-type antimicrobial and antitumor agent produced by Streptomyces argillaceus. Modifying post-polyketide synthase (PKS) tailoring enzymes involved in the production of mithramycin effective way gaining further information regarding late steps its biosynthetic pathway. In addition, new "unnatural" natural products class are likely to be produced. The role two such post-PKS enzymes, encoded mtmC mtmTIII, was investigated, four novel acid drugs, premithramycin-type...
Abstract Recent developments in stem cell biology have enabled the study of fate decisions early human development that are impossible to vivo . However, understanding how varies across individuals and, particular, influence common genetic variants during this process has not been characterised. Here, we exploit iPS lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing population variation endoderm differentiation. We identify molecular markers predictive...
Understanding pancreatic development is instrumental to diabetes research and β-cell replacement therapies. Here, we investigate Glucocorticoid Receptor (GR) signaling during early pancreas in mice humans. Previous reports suggest that glucocorticoids do not play a significant role mouse before the second transition. In this study, demonstrate that, under physiological conditions, GR selectively active pro-acinar endocrine cells from E11.5, silenced bipotent progenitors, reactivated...
The production of epothilone mixtures is a direct consequence the substrate tolerance module 3 acyltransferase (AT) domain polyketide synthase (PKS) which utilises both malonyl- and methylmalonyl-CoA extender units. Particular amino acid motifs in active site AT domains influence selection for (YASH) or malonyl-CoA (HAFH). This motif appears hybrid form (HASH) epoAT3 may represent molecular basis relaxed specificity domain. To investigate this possibility from modules 2 PKS were examined...
Limited proteolysis in combination with liquid chromatography‐ion trap mass spectrometry (LC‐MS) was used to analyze engineered or natural proteins derived from a type I modular polyketide synthase (PKS), the 6‐deoxyerythronolide B (DEBS), and comprising either first two extension modules linked chain‐terminating thioesterase (TE) (DEBS1‐TE); last (DEBS3) module TE (diketide synthase, DKS). Functional domains were released by controlled proteolysis, exact boundaries of obtained through...
Mithramycin is an antitumor aromatic polyketide synthesized by Streptomyces argillaceus. Two genes (mtrX and mtrY) of the mithramycin gene cluster were inactivated replacement. Inactivation mtrX, that encodes ABC excission nuclease system for DNA repair, produced a mutant was affected in normal rate growth. Expression mtrX albus multicopy plasmid vector conferred low increase resistance to mithramycin. mtrY, protein unknown function, 50% decrease biosynthesis. When mtrY expressed wild-type...
Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and locally advanced or concurrent metastases. The aggressive phenotype relative chemo- radiotherapeutic resistance PDAC is thought to be mediated largely by its prominent stroma, which supported an extracellular matrix (ECM). Therefore, we investigated the impact tissue-matched human ECM in driving role promoting chemotherapy resistance. Decellularized pancreata livers were recellularized PANC-1...
Polyketide derivatives, such as 1, are obtained in enhanced yield from added benzoate by coexpressing Saccharopolyspora erythraea a hybrid erythromycin–soraphen polyketide synthase (PKS) together with benzoate:CoA ligase the enterocin-producing (enc) pathway of marine streptomycete. Remarkably, coexpression single gene encP encoding phenylalanine ammonia lyase is sufficient to produce PKS primer benzoyl-CoA S. endogenous L-phenylalanine without any need supply precursors medium.
ABSTRACT Background and aims Non-alcoholic fatty liver disease (NAFLD) is a major health care challenge new therapies are urgently needed. However, the mechanisms underlying remain to be understood. Indeed, studying NAFLD remains challenging due lack of model systems recapitulating different aspects human pathology. Human induced pluripotent stem cells (hiPSCs) offer unique opportunity address this limitation since they can differentiated into large quantity cells. Here, we took advantage...
Non-alcoholic fatty liver disease (NAFLD) is a major health care challenge and new therapies are urgently needed. However, the mechanisms underlying remain to be understood. Indeed, studying NAFLD remains challenging due lack of model systems recapitulating different aspects human pathology. Human induced pluripotent stem cells (hiPSCs) offer unique opportunity address this limitation since they can differentiated into large quantity cells. Here, we took advantage hiPSCs develop...
Non-alcoholic fatty liver disease (NAFLD) is a major health care challenge and new therapies are urgently needed. However, the mechanisms underlying remain to be understood. Indeed, studying NAFLD remains challenging due lack of model systems recapitulating different aspects human pathology. Human induced pluripotent stem cells (hiPSCs) offer unique opportunity address this limitation since they can differentiated into large quantity cells. Here, we took advantage hiPSCs develop...
The liver has been studied extensively due to the broad number of diseases affecting its vital functions. However, therapeutic advances, especially in regenerative medicine, are currently hampered by lack knowledge concerning human hepatic cell development. Here, we addressed this limitation describing developmental trajectories different types comprising fetal at single-cell resolution. These transcriptomic analyses revealed that sequential cell-to-cell interactions direct functional...
ABSTRACT Haematopoietic stem cells (HSC) first arise during development in the aorta-gonad-mesonephros (AGM) region of embryo from a population haemogenic endothelial which undergo endothelial-to-haematopoietic transition (EHT). Despite progress achieved recent years, molecular mechanisms driving EHT are still poorly understood, especially human where AGM is not easily accessible. In this study, we took advantage pluripotent cell (hPSC) differentiation system and single-cell transcriptomics...