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Your search keyword '"RIKEN Center for Life Science Technologies (RIKEN CLST)"' showing total 13 results
Start Over Author "RIKEN Center for Life Science Technologies (RIKEN CLST)" Topic 030104 developmental biology
13 results on '"RIKEN Center for Life Science Technologies (RIKEN CLST)"'

1. Astrocytic IP3Rs: Beyond IP3R2

Author

Mark W. Sherwood, Misa Arizono, Aude Panatier, Katsuhiko Mikoshiba, Stéphane H. R. Oliet, Oliet, Stephane, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), ShanghaiTech University [Shanghai], Toho University, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, and Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm)

Subjects
0301 basic medicine, Gene isoform, [SDV]Life Sciences [q-bio], Mini Review, Neurosciences. Biological psychiatry. Neuropsychiatry, Biology, Neurotransmission, inositol triphosphate (IP3) receptor, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, astrocyte, GPCR, Tripartite synapse, medicine, Receptor, G protein-coupled receptor, calcium, tripartite synapse, Glutamate receptor, gliotransmission, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, IP 3 R subtypes, IP3R subtypes, Cellular Neuroscience, Synaptic plasticity, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery, Astrocyte, RC321-571
Abstract

Astrocytes are sensitive to ongoing neuronal/network activities and, accordingly, regulate neuronal functions (synaptic transmission, synaptic plasticity, behavior, etc.) by the context-dependent release of several gliotransmitters (e.g., glutamate, glycine, D-serine, ATP). To sense diverse input, astrocytes express a plethora of G-protein coupled receptors, which couple, via Gi/o and Gq, to the intracellular Ca2+ release channel IP3-receptor (IP3R). Indeed, manipulating astrocytic IP3R-Ca2+ signaling is highly consequential at the network and behavioral level: Depleting IP3R subtype 2 (IP3R2) results in reduced GPCR-Ca2+ signaling and impaired synaptic plasticity; enhancing IP3R-Ca2+ signaling affects cognitive functions such as learning and memory, sleep, and mood. However, as a result of discrepancies in the literature, the role of GPCR-IP3R-Ca2+ signaling, especially under physiological conditions, remains inconclusive. One primary reason for this could be that IP3R2 has been used to represent all astrocytic IP3Rs, including IP3R1 and IP3R3. Indeed, IP3R1 and IP3R3 are unique Ca2+ channels in their own right; they have unique biophysical properties, often display distinct distribution, and are differentially regulated. As a result, they mediate different physiological roles to IP3R2. Thus, these additional channels promise to enrich the diversity of spatiotemporal Ca2+ dynamics and provide unique opportunities for integrating neuronal input and modulating astrocyte–neuron communication. The current review weighs evidence supporting the existence of multiple astrocytic-IP3R isoforms, summarizes distinct sub-type specific properties that shape spatiotemporal Ca2+ dynamics. We also discuss existing experimental tools and future refinements to better recapitulate the endogenous activities of each IP3R isoform.

Published
2021
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2. Multi‐omics analysis of hiPSCs‐derived HLCs matured on‐chip revealed patterns typical of liver regeneration

Author

Yukio Kato, Hiroyuki Kusuhara, Françoise Gilard, Johanna Bruce, Daiki Mori, Marjorie Leduc, Hiroshi Arakawa, Atsushi Miyajima, Stéphane Poulain, Karin Araya, Taketomo Kido, Mathieu Danoy, Morgane Le Gall, Charles Plessy, Eric Leclerc, Rachid Jellali, Yasuyuki Sakai, Yannick Tauran, Laboratory for Integrated Micro Mechatronics Systems (LIMMS), The University of Tokyo (UTokyo)-Centre National de la Recherche Scientifique (CNRS), The University of Tokyo (UTokyo), Laboratoire des Multimatériaux et Interfaces (LMI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Biomécanique et Bioingénierie (BMBI), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), Plateforme protéomique 3P5 [Institut Cochin] (3P5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Kanazawa University (KU), Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science 16H06328, ANR-16-RHUS-0005,iLite,iLite(2016), JELLALI, RACHID, iLite - - iLite2016 - ANR-16-RHUS-0005 - RHUS - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0106 biological sciences, 0301 basic medicine, Induced Pluripotent Stem Cells, iPSCs, Bioengineering, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Proteomics, liver, 01 natural sciences, Applied Microbiology and Biotechnology, Transcriptome, 03 medical and health sciences, transcriptomics, Metabolomics, proteomics, 010608 biotechnology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, Induced pluripotent stem cell, Biochip, Regeneration (biology), nanoCAGE, Cell Differentiation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Genomics, differentiation, metabolomics, Liver regeneration, In vitro, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Liver Regeneration, Cell biology, 030104 developmental biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], hepatocytes, organ-on-chip, Biotechnology
Abstract

International audience; Maturation of human-induced pluripotent stem cells (hiPSCs)-derived hepatocytes-like cells (HLCs) toward a complete hepatocyte phenotype remains a challenge as primitiveness patterns are still commonly observed. In this study, we propose a modified differentiation protocol for those cells which includes a prematuration in Petri dishes and a maturation in microfluidic biochip. For the first time, a large range of biomolecular families has been extracted from the same sample to combine transcriptomic, proteomic, and metabolomic analysis. After integration, these datasets revealed specific molecular patterns and highlighted the hepatic regeneration profile in biochips. Overall, biochips exhibited processes of cell proliferation and inflammation (via TGFB1) coupled with anti-fibrotic signaling (via angiotensin 1-7, ATR-2, and MASR). Moreover, cultures in this condition displayed physiological lipid-carbohydrate homeostasis (notably via PPAR, cholesterol metabolism, and bile synthesis) coupled with cell respiration through advanced oxidative phosphorylation (through the overexpression of proteins from the third and fourth complex). The results presented provide an original overview of the complex mechanisms involved in liver regeneration using an advanced in vitro organ-on-chip technology.

Published
2021
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3. Analysis of hiPSCs differentiation toward hepatocyte-like cells upon extended exposition to oncostatin

Author

Hiroshi Arakawa, Hiroyuki Kusuhara, Yukio Kato, Eric Leclerc, Mathieu Danoy, Karin Araya, Yasuyuki Sakai, Charles Plessy, Taketomo Kido, Yannick Tauran, Stéphane Poulain, Sachi Kato, Atsushi Miyajima, Daiki Mori, Laboratory for Integrated Micro Mechatronics Systems (LIMMS), The University of Tokyo (UTokyo)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Multimatériaux et Interfaces (LMI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Ressources Biologiques - [Nancy] (CRB Nancy), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), The University of Tokyo (UTokyo), Laboratory of Pharmacokinetics, Kanazawa University (KU), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomécanique et génie biomédical (BIM), and Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, Drug Evaluation, Preclinical, Oncostatin M, Biology, Transcriptome, Cytochrome P-450 CYP2C8, 03 medical and health sciences, 0302 clinical medicine, Cytochrome P-450 CYP1A2, medicine, Cytochrome P-450 CYP3A, Humans, NRF1, Induced pluripotent stem cell, Molecular Biology, Transcription factor, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Nuclear Respiratory Factor 1, Liver cell, Cell Differentiation, Cell Biology, Liver regeneration, 3. Good health, HNF1A, Cell biology, Liver Regeneration, Cytochrome P-450 CYP2B6, 030104 developmental biology, medicine.anatomical_structure, Sp3 Transcription Factor, Cytochrome P-450 CYP2D6, Liver, Hepatocyte, Hepatocytes, 030217 neurology & neurosurgery, Developmental Biology
Abstract

The capability to produce and maintain functional human adult hepatocytes remains one of the major challenges for the use of in-vitro models toward liver cell therapy and industrial drug-screening applications. Among the suggested strategies to solve this issue, the use of human-induced pluripotent stem cells (hiPSCs), differentiated toward hepatocyte-like cells (HLCs) is promising. In this work, we propose a 31-day long protocol, that includes a final 14-day long phase of oncostatin treatment, as opposed to a 7-day treatment which led to the formation of a hepatic tissue functional for CYP1A2, CYP2B6, CYP2C8, CYP2D6, and CYP3A4. The production of albumin, as well as bile acid metabolism and transport, were also detected. Transcriptome profile comparisons and liver transcription factors (TFs) motif dynamics revealed increased expression of typical hepatic markers such as HNF1A and of important metabolic markers like PPARA. The performed analysis has allowed for the extraction of potential targets and pathways which would allow enhanced hepatic maturation in-vitro. From this investigation, NRF1 and SP3 appeared as transcription factors of importance. Complex epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) patterns were also observed during the differentiation process. Moreover, whole transcriptome analysis highlighted a response typical of the one observed in liver regeneration and hepatocyte proliferation. While a complete maturation of hepatocytes was yet to be obtained, the results presented in this work provide new insights into the process of liver development and highlight potential targets aimed to improve in-vitro liver regeneration.

Published
2020
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4. Optimized protocol for the hepatic differentiation of induced pluripotent stem cells in a fluidic microenvironment

Author

Stéphane Poulain, Myriam Lereau Bernier, Hiroyuki Kusuhara, Taketomo Kido, Eric Leclerc, Sachi Kato, Mathieu Danoy, Charles Plessy, Daiki Mori, Atsushi Miyajima, Yasuyuki Sakai, Keiichi Kimura, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, The University of Tokyo (UTokyo), and Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, 0301 basic medicine, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, Bioengineering, 01 natural sciences, Applied Microbiology and Biotechnology, Transcriptome, Extracellular matrix, 03 medical and health sciences, 010608 biotechnology, CEBPA, Humans, Progenitor cell, Stem Cell Niche, Biochip, Induced pluripotent stem cell, Transcription factor, ComputingMilieux_MISCELLANEOUS, Chemistry, Cell Differentiation, TCF4, Hep G2 Cells, Microfluidic Analytical Techniques, Cell biology, 030104 developmental biology, Gene Expression Regulation, Liver, Hepatocytes, Biotechnology, Transcription Factors
Abstract

In the present study, we evaluated the performance of different protocols for the hepatic differentiation of human-induced pluripotent stem cells (hiPSCs) in microfluidic biochips. Strategies for complete and partial on-chip differentiation were tested. Unlike full on-chip differentiation, the transfer of iPSCs from Petri dishes to biochips during the differentiation process produced a heterogeneous tissue with enhanced hepatic features compared with control cultures in Petri dishes. The tissue in biochips was constituted of cells expressing either stabilin-1 or albumin, while no stabilin-1 was detected in controls. Functional analysis also revealed double the production rate for albumin in biochips (about 2,000 ng per day per 106 cells). Besides this, tissues obtained in biochips and controls exhibited the metabolism of a specific bile acid. Whole transcriptome analysis with nanoCAGE exhibited a differential expression of 302 genes between control and biochip cultures and a higher degree of hepatic differentiation in biochips, together with increased promoter motif activity for typical liver transcription factors such as estrogen related receptor alpha ( ESRRA), hepatic nuclear factor 1 ( HNF1A), hepatic nuclear factor 4 ( HNF4A), transcription factor 4 ( TCF4), and CCAAT enhancer binding protein alpha ( CEBPA). Gene set enrichment analysis identified several pathways related to the extracellular matrix, tissue reorganization, hypoxia-inducible transcription factor, and glycolysis that were differentially modulated in biochip cultures. However, the presence of CK19/ALB-positive cells and the ɑ-fetoprotein levels measured in the cultures still reflect primitive differentiation patterns. Overall, we identified key parameters for improved hepatic differentiation on-chip, including the maturation stage of hepatic progenitors, inoculation density, adhesion time, and perfusion flow rate. Optimization of these parameters further led to establish a protocol for reproducible differentiation of hiPSCs into hepatocyte-like cells in microfluidic biochips with significant improvements over Petri dish cultures.

Published
2019
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5. Amphioxus functional genomics and the origins of vertebrate gene regulation

Author

Patrick Wincker, Pierre Pontarotti, Elisa de la Calle-Mustienes, Zbynek Kozmik, Malcolm Perry, José Luis Gómez-Skarmeta, Cristian Cañestro, Stéphanie Bertrand, Yamile Marquez, Èlia Benito-Gutiérrez, Juan J. Tena, Hector Escriva, Alexandra Louis, Anthony Leon, Matthew T. Weirauch, Juan Ramón Martínez-Morales, Panos N. Firbas, Peter W. H. Holland, Iryna Kozmikova, Daniel Aldea, Sandra Jiménez-Gancedo, Jordi Garcia-Fernàndez, Jean-Marc Aury, Michael Schubert, Paul Edward Duckett, Beatriz Albuixech-Crespo, Simon J. van Heeringen, Boris Lenhard, Piero Carninci, Carlos Herrera-Úbeda, Olivier Mirabeau, Demian Burguera, Lorena Buono, Tokiharu Takahashi, Rafael D. Acemel, Silvia Naranjo, Ryan Lister, Sophie Mangenot, Lucie Subirana, Ksenia Skvortsova, Jr-Kai Yu, Hugues Roest Crollius, Ildiko M. L. Somorjai, Vincent Laudet, Piotr J. Balwierz, Gabriel A. B. Marais, Ignacio Maeso, Anlong Xu, Christopher D. R. Wyatt, Shengfeng Huang, Ozren Bogdanovic, David E. K. Ferrier, Ferdinand Marlétaz, Salvatore D'Aniello, Jon Permanyer, Filipe Castro, Manuel Irimia, Ricard Albalat, Yann Le Petillon, Ensieh Farahani, Hervé Seitz, Okinawa Institute of Science and Technology Graduate University (OIST), Department of Zoology [Oxford], University of Oxford, Centro Andaluz de Biología del Desarrollo, Universidad Pablo Olavide, University of New South Wales [Sydney] (UNSW), The University of Western Australia (UWA), Imperial College London, Universitat Pompeu Fabra [Barcelona] (UPF), Biologie intégrative des organismes marins (BIOM), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Barcelona Institute of Science and Technology (BIST), Universidad Pablo de Olavide [Sevilla] (UPO), Radboud University [Nijmegen], University of Barcelona, Garvan Institute of medical research, Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS), Czech Academy of Sciences [Prague] (CAS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Genetics and IrBio, University of Cambridge [UK] (CAM), Universidade do Porto = University of Porto, Stazione Zoologica Anton Dohrn (SZN), University of St Andrews [Scotland], Sun Yat-Sen University [Guangzhou] (SYSU), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Manchester [Manchester], Université Paris sciences et lettres (PSL), Academia Sinica, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), University of Cincinnati (UC), University of Bergen (UiB), ANR-16-CE12-0008,CHORELAND,Détermination de la conservation du landscape génomique de régulation au cours de l'embryogenèse des chordés(2016), European Project: 637591,H2020,ERC-2014-STG,NEURAL AS(2015), European Project: 658521,H2020,H2020-MSCA-IF-2014,EVOREL(2016), European Project: 268513,EC:FP7:ERC,ERC-2010-AdG_20100317,GENEVA(2011), European Commission, The Leverhulme Trust, University of St Andrews. School of Biology, University of St Andrews. Marine Alliance for Science & Technology Scotland, University of St Andrews. Scottish Oceans Institute, University of St Andrews. Biomedical Sciences Research Complex, University of Oxford [Oxford], Radboud university [Nijmegen], Garvan Institute of Medical Research, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Universidade do Porto, Commission of the European Communities, Biotechnology and Biological Sciences Research Council (BBSRC), Wellcome Trust, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Departament de Genetica, Facultat de Biologia, Universitat de Barcelona (UB), Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Científicas, Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Max F. Perutz Laboratories, University of Vienna [Vienna], DYnamique et Organisation des GENomes - Equipe de l'IBENS (DYOGEN), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Unité de Biométrie et Intelligence Artificielle (UBIA), Institut National de la Recherche Agronomique (INRA), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Departament de Genètica, Universitat Autònoma de Barcelona [Barcelona] (UAB), Texas A&M University [College Station], Sun Yat-Sen University (SYSU), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sexe et évolution, Département PEGASE [LBBE] (PEGASE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Analyse, Topologie, Probabilités (LATP), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Medical Sciences / Beijing, Institute of Cellular and Organismic Biology, Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, RIKEN, Centre of Excellence in Plant Energy Biology (ARC), Australian National University (ANU)-School of Biochemistry and Molecular Biology, SARS International Centre for Marine Molecular Biology, Modèles en biologie cellulaire et évolutive (MBCE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), European Research Council, Ministerio de Economía y Competitividad (España), Australian Research Council, Maeso, Ignacio [0000-0002-6440-8457], Tena, Juan J [0000-0001-8165-7984], Perry, Malcolm [0000-0001-5228-3434], Wyatt, Christopher DR [0000-0001-8033-2213], de la Calle-Mustienes, Elisa [0000-0002-8975-6503], Bertrand, Stephanie [0000-0002-0689-0126], Naranjo, Silvia [0000-0002-4529-3332], Jimenez-Gancedo, Sandra [0000-0002-2247-1319], Aldea, Daniel [0000-0001-5101-0194], Buono, Lorena [0000-0002-5457-4515], Louis, Alexandra [0000-0001-7032-5650], Balwierz, Piotr J [0000-0002-1548-4605], Aury, Jean-Marc [0000-0003-1718-3010], Albalat, Ricard [0000-0003-0282-9595], Benito-Gutiérrez, Èlia [0000-0003-2435-0948], Cañestro, Cristian [0000-0003-4623-8105], Castro, Filipe [0000-0001-7697-386X], Ferrier, David EK [0000-0003-3247-6233], Schubert, Michael [0000-0002-2341-712X], Seitz, Hervé [0000-0001-8172-5393], Somorjai, Ildiko [0000-0001-5243-6664], Takahashi, Tokiharu [0000-0002-5785-8660], Yu, Jr-Kai [0000-0001-8591-0529], Carninci, Piero [0000-0001-7202-7243], Martinez-Morales, Juan Ramon [0000-0002-4650-4293], Garcia-Fernàndez, Jordi [0000-0001-5677-5970], Lister, Ryan [0000-0001-6637-7239], Escriva, Hector [0000-0001-7577-5028], Irimia, Manuel [0000-0002-2179-2567], Apollo - University of Cambridge Repository, CIIMAR - Centro Interdisciplinar de Investigação Marinha e Ambiental, COMBE, Isabelle, Détermination de la conservation du landscape génomique de régulation au cours de l'embryogenèse des chordés - - CHORELAND2016 - ANR-16-CE12-0008 - AAPG2016 - VALID, Functions and evolutionary impact of transcriptomic novelties in the vertebrate brain - NEURAL AS - - H20202015-04-01 - 2020-03-31 - 637591 - VALID, Evolution of Regulatory Landscapes in Chordates - EVOREL - - H20202016-01-01 - 2017-12-31 - 658521 - VALID, Genome Evolution in the Animal Kingdom - GENEVA - - EC:FP7:ERC2011-06-01 - 2016-05-31 - 268513 - VALID, Institute of Molecular Genetics of the Czech Academy of Sciences, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) - Grenoble, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Marseille (I2M), Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Riken Omics Science Center, Riken Yokohama Institute, Cincinnati Children's Hospital Medical Center, and Computational Regulatory Genomics

Subjects
Epigenomics, Branchiostoma, genetic analysis, animal cell, transcriptomics, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, vertebrate, zebra fish, histone modification, Branchiostoma lanceolatum, ComputingMilieux_MISCELLANEOUS, comparative study, Lancelets, Regulation of gene expression, DDC model, DNA methylation, adult, Vertebrate, Genomics, priority journal, Science & Technology - Other Topics, Molecular Developmental Biology, LANDSCAPES, whole genome duplication, Functional genomics, chordate evolution, CONSERVATION, embryo, gene sequence, PLURIPOTENCY, Article, animal tissue, 03 medical and health sciences, regulatory genomics, biology.animal, genomics, Humans, genome, mouse, Science & Technology, Molecular Sequence Annotation, TRANSGENESIS, DNA Methylation, Ancestral expression, developmental stage, 030104 developmental biology, hourglass model, Amfiox, Evolutionary biology, molecular genetics, chromatin, Subfunctionalization, transcriptome, 030217 neurology & neurosurgery, CHROMATIN, 0301 basic medicine, Branchiostoma Lanceolatum, Genome, specialization, Gene duplication, Vertebrats, Promoter Regions, Genetic, Whole-genome Duplication (WGD), Multidisciplinary, gene control, BRANCHIOSTOMA-LANCEOLATUM, innovation, Multidisciplinary Sciences, female, SEQ, Vertebrates, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Phylotypic Period, General Science & Technology, invertebrate, QH426 Genetics, Biology, DNA DEMETHYLATION, male, evolution, Animals, controlled study, gene, QH426, multigene family, Body Patterning, Vertebrata, nonhuman, Amphioxus, ZEBRAFISH, gene duplication, embryo development, DAS, biology.organism_classification, EVOLUTION, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Gene Expression Regulation, gene expression, Molecular evolution, Transcriptome
Abstract

Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that—in vertebrates—over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations., This research was funded primarily by the European Research Council (ERC) under the European Union’s Horizon 2020 and Seventh Framework Program FP7 research and innovation programs (ERC-AdG-LS8-740041 to J.L.G.-S., ERC-StG-LS2-637591 to M.I., a Marie Sklodowska-Curie Grant (658521) to I.M. and a FP7/2007-2013-ERC-268513 to P.W.H.H.), the Spanish Ministerio de Economía y Competitividad (BFU2016-74961-P to J.L.G.-S., RYC-2016-20089 to I.M., BFU2014-55076-P and BFU2017-89201-P to M.I. and BFU2014-55738-REDT to J.L.G.-S, M.I. and J.R.M.-M), the ‘Centro de Excelencia Severo Ochoa 2013-2017’(SEV-2012-0208), the ‘Unidad de Excelencia María de Maetzu 2017-2021’(MDM-2016-0687), the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program FP7 under REA grant agreement number 607142 (DevCom) to J.L.G.-S., and the CNRS and the ANR (ANR16-CE12-0008-01) to H.E. O.B. was supported by an Australian Research Council Discovery Early Career Researcher Award (DECRA; DE140101962).

Published
2018
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6. Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress

Author

Diego di Bernardo, Ali Tebbi, Annamaria Carissimo, Kosuke Hashimoto, Piero Carninci, Florence Levillayer, Nesrine Boudjadja, Yu Wei, Hugo Varet, Grégory Jouvion, Laurence Fiette, Guillaume Soubigou, Stefano Cairo, Ana Maria Suzuki, Pathogenèse des Virus de l'Hépatite B (PVHB), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hépacivirus et Immunité innée, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris] (IP), Centre d'Informatique pour la Biologie, XenTech, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Telethon Institute of Genetics and Medicine, European Union’s Seventh Framework Program (FP7) under grant agreement No. 259743 (MODHEP consortium) to the Institut Pasteur (A.T., F.L., Y.W.), RIKEN Center (K.H., A.M.S., P.C.) and Telethon Institute of Genetics and Medicine (D.B.)., European Project: 259743,EC:FP7:HEALTH,FP7-HEALTH-2010-two-stage,MODHEP(2011), Wei, Yu, Systems biology of liver cancer: an integrative genomic-epigenomic approach - MODHEP - - EC:FP7:HEALTH2011-01-01 - 2016-06-30 - 259743 - VALID, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris], Tebbi, Ali, Levillayer, Florence, Jouvion, Grégory, Fiette, Laurence, Soubigou, Guillaume, Varet, Hugo, Boudjadja, Nesrine, Cairo, Stefano, Hashimoto, Kosuke, Suzuki, Ana Maria, Carninci, Piero, Carissimo, Annamaria, and DI BERNARDO, Diego

Subjects
0301 basic medicine, Male, Cancer Research, Nude, Apoptosis, medicine.disease_cause, Cell Transformation, Lipid peroxidation, chemistry.chemical_compound, Mice, Adenomatous Polyposis Coli, Animals, Cell Transformation, Neoplastic, Cells, Cultured, DNA Damage, Female, Fibroblasts, Intestinal Neoplasms, Lipid Peroxidation, Liver, Mice, Inbred BALB C, Mice, Knockout, Mice, Nude, Oxidative Stress, P-Glycoproteins, Reactive Oxygen Species, Inbred BALB C, Cultured, Bile acid, General Medicine, 3. Good health, Biochemistry, ATP Binding Cassette Transporter, Subfamily B, DNA damage, medicine.drug_class, Cells, Knockout, [SDV.CAN]Life Sciences [q-bio]/Cancer, Original Manuscript, Biology, NO, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Lipid biosynthesis, medicine, Neoplastic, Fatty acid metabolism, Microarray analysis techniques, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, HCCS, Molecular biology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030104 developmental biology, chemistry, Carcinogenesis
Abstract

Summary The transporter of phosphatidylcholine Mdr2/MDR3 not only plays an essential role for bile formation but also is involved in the maintenance of lipid homeostasis. Deficiency of Mdr2 leads to accumulation of ROS, cell transformation and susceptibility to intestinal carcinogenesis., Multidrug resistance 2 (Mdr2), also called adenosine triphosphate-binding cassette B4 (ABCB4), is the transporter of phosphatidylcholine (PC) at the canalicular membrane of mouse hepatocytes, which plays an essential role for bile formation. Mutations in human homologue MDR3 are associated with several liver diseases. Knockout of Mdr2 results in hepatic inflammation, liver fibrosis and hepatocellular carcinoma (HCC). Whereas the pathogenesis in Mdr2 −/− mice has been largely attributed to the toxicity of bile acids due to the absence of PC in the bile, the question of whether Mdr2 deficiency per se perturbs biological functions in the cell has been poorly addressed. As Mdr2 is expressed in many cell types, we used mouse embryonic fibroblasts (MEF) derived from Mdr2 −/− embryos to show that deficiency of Mdr2 increases reactive oxygen species accumulation, lipid peroxidation and DNA damage. We found that Mdr2 −/− MEFs undergo spontaneous transformation and that Mdr2 −/− mice are more susceptible to chemical carcinogen-induced intestinal tumorigenesis. Microarray analysis in Mdr2−/− MEFs and cap analysis of gene expression in Mdr2 −/− HCCs revealed extensively deregulated genes involved in oxidation reduction, fatty acid metabolism and lipid biosynthesis. Our findings imply a close link between Mdr2 −/−-associated tumorigenesis and perturbation of these biological processes and suggest potential extrahepatic functions of Mdr2/MDR3.

Published
2015
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7. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author

de Rie, Yoko, Abugessaisa, Yoko, Alam, Tanvir, Arner, Yoko, Arner, Peter, Ha, Haitham, Aström, Gaby, Babina, Magda, Bertin, Yoko, Burroughs, Yoko, Carlisle, Ailsa, Daub, Yoko, Detmar, Michael, Deviatiiarov, Yoko, Fort, Yoko, Gebhard, Claudia, Goldowitz, Daniel, Guhl, Sven, Ha, Thomas, Harshbarger, Yoko, Hasegawa, Yoko, Hashimoto, Yoko, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly, Hon, Yoko, Huang, Edward, Ishizu, Yoko, Kai, Chieko, Kasukawa, Yoko, Klinken, Peter, Lassmann, Yoko, Lecellier, Charles-Henri, Lee, Weonju, Lizio, Yoko, Makeev, Vsevolod, Mathelier, Anthony, Medvedeva, Yulia, Mejhert, Niklas, Mungall, Christopher, Noma, Yoko, Ohshima, Mitsuhiro, Okada-Hatakeyama, Yoko, Persson, Helena, Rizzu, Patrizia, Roudnicky, Filip, Sætrom, Pål, Sato, Hiroki, Severin, Yoko, Shin, Yoko, Swoboda, Rolf, Tarui, Yoko, Toyoda, Hiroo, Vitting-Seerup, Kristoffer, Winteringham, Louise, Yamaguchi, Yoko, Yasuzawa, Kayoko, Yoneda, Misako, Yumoto, Noriko, Zabierowski, Susan, Zhang, Peter, Wells, Christine, Summers, Kim, Kawaji, Hideya, Sandelin, Albin, Rehli, Michael, Hayashizaki, Yoshihide, Carninci, Piero, Forrest, Alistair, de Hoon, Michiel, de Rie, Derek, Abugessaisa, Imad, Arner, Erik, Ashoor, Haitham, Bertin, Nicolas, Burroughs, A Maxwell, Daub, Carsten, Deviatiiarov, Ruslan, Fort, Alexandre, Ha, Jayson, Ha, Akira, Ha, Kosuke, Hon, Chung Chau, Ishizu, Yuri, Kasukawa, Takeya, Lassmann, Timo, Lizio, Marina, Noma, Shohei, Ha, Mariko, Severin, Jessica, Shin, Jay, Tarui, Hiroshi, Ha, Yoshihide, Computat Biosci Res Ctr, Comp Elect & Math Sci & Engn Div, King Abdullah University of Science and Technology (KAUST), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Dept Dermatol & Allergy, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Clinical Genetics, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institute of Genetics and Selection of Industrial Microorganisms, GosNIIGenetika, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Oncology, Lund University [Lund]-Clinical Sciences, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), University of Copenhagen = Københavns Universitet (KU), Cold Spring Harbor Laboratory, RIKEN Center for Life Science Technologies (RIKEN CLST), Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, Karolinska Institutet [Stockholm], Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Riken Omics Science Center, and Riken Yokohama Institute

Subjects
0301 basic medicine, FANTOM Consortium, Cells, Biomedical Engineering, Bioengineering, Biology, Applied Microbiology and Biotechnology, Genome, Article, Promoter Regions, 03 medical and health sciences, Mice, Genetic, Transcription (biology), metabolism [MicroRNAs], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Gene expression, Transcriptional regulation, Gene silencing, Animals, Humans, genetics [MicroRNAs], Promoter Regions, Genetic, Cells, Cultured, Gene Library, Genetics, Cultured, Gene Expression Profiling, RNA, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, Gene expression profiling, MicroRNAs, 030104 developmental biology, Good Health and Well Being, genetics [Promoter Regions, Genetic], ddc:660, Molecular Medicine, Generic health relevance, Biotechnology, methods [Gene Expression Profiling]
Abstract

International audience; MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

Published
2017
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8. Capillary-Inserted Rotor Design for HRµMAS NMR-Based Metabolomics on Mass-Limited Neurospheres

Author

Yosky Kataoka, Alan Wong, Masayuki Nakano, Yasuhisa Tamura, Masanori Yamato, Satoshi Kume, Nghia Tuan Duong, Yusuke Nishiyama, Advanced Solid-State NMR Unit (RIKEN CLST-JEOL), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Multi-Modal Microstructure Analysis Unit (RIKEN CLST-JEOL), RIKEN Center for Life Science Technologies (RIKEN CLST), Osaka City University Graduate Medical School, Laboratoire Structure et Dynamique par Résonance Magnétique (LCF) (LSDRM), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), JEOL Ltd, 1156 Nakagami, Akishima, Tokyo 196-0022, Japan., ANR-16-CE11-0023,HRmicroMAS,SPECTROSCOPIE RMN MICROSCOPIC SPECIMENS(2016), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Magnetic Resonance Spectroscopy, Capillary action, Analytical chemistry, Pharmaceutical Science, capillary-inserted rotor, Standard solution, 01 natural sciences, Article, Spectral line, Analytical Chemistry, law.invention, lcsh:QD241-441, 03 medical and health sciences, Nuclear magnetic resonance, Metabolomics, lcsh:Organic chemistry, law, Drug Discovery, mass-limited neurospheres, Magic angle spinning, Physical and Theoretical Chemistry, Spectroscopy, NMR, metabolomics, metabolites, HRµMAS, Rotor (electric), Chemistry, 010401 analytical chemistry, Organic Chemistry, Analytical technique, [CHIM.MATE]Chemical Sciences/Material chemistry, 0104 chemical sciences, 030104 developmental biology, Chemistry (miscellaneous), Molecular Medicine
Abstract

International audience; Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique and has been widely used in metabolomics. However, the intrinsic low sensitivity of NMR prevents its applications to systems with limited sample availabilities. In this study, a new experimental approach is presented to analyze mass-scarce samples in limited volumes of less than 300 nL with simple handling. The sample is loaded into the glass capillary, and this capillary is then inserted into a Kel-F rotor. The experimental performance of the capillary-inserted rotor (capillary-insert) is investigated on an isotropic solution of sucrose by the use of a high-resolution micro-sized magic angle spinning (HRµMAS) probe. The acquired NMR signal's sensitivity to a given sample amount is comparable or even higher in comparison to that recorded by the standard solution NMR probe. More importantly, this capillary-insert coupled with the HRµMAS probe allows in-depth studies of heterogeneous samples as the MAS removes the line broadening caused by the heterogeneity. The NMR analyses of mass-limited cultured neurospheres have been demonstrated, resulting in high quality spectra where numerous metabolites are unambiguously identified.

Published
2017
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9. A three-dimensional movie of structural changes in bacteriorhodopsin

Author

Eriko Nango, Jörg Standfuss, Shigeki Owada, Takanori Nakane, Petra Båth, Robert Dods, Ayumi Yamashita, Byeonghyun Jeon, Minoru Kubo, Takaaki Fujiwara, Jan Davidsson, Rebecka Andersson, Dohyun Im, Michihiro Sugahara, Yasuaki Yamanaka, Kazumasa Oda, Makina Yabashi, Osamu Nureki, Takaki Hatsui, Kensuke Tono, Tomoyuki Tanaka, Michio Murata, Gebhard F. X. Schertler, Antoine Royant, Daewoong Nam, Takashi Nomura, Eiichi Mizohata, Satoshi Kawatake, Tetsunari Kimura, So Iwata, Przemyslaw Nogly, Tatsuro Shimamura, Takashi Kameshima, Changyong Song, Masahiro Fukuda, Jun Kobayashi, Shigeru Matsuoka, Yasumasa Joti, Ana-Nicoleta Bondar, Richard Neutze, Cecilia Wickstrand, Toshiaki Hosaka, Rie Tanaka, Toshi Arima, Tomohiro Nishizawa, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), Department of Biological Sciences, The University of Tokyo (UTokyo), Department of Chemistry and Molecular Biology [Gothenburg], University of Gothenburg (GU), Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Department of Applied Chemistry, Osaka University [Osaka], Division of Biology and Chemistry, Laboratory for Biomolecular Research, Paul Scherrer Institute (PSI), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Physics, Pohang University of Science and Technology (POSTECH), Department of Cell Biology, Graduate School of Medicine, Kyoto University [Kyoto], Angström Laboratory, Uppsala University, JST-Exploratory Research for Advanced Technology (ERATO), Japan Synchrotron Radiation Research Institute [Hyogo] (JASRI), Theoretical Molecular Biophysics, Department of Physics, Freie Universität Berlin, ANR-11-JSV5-0009,SOxygen,Oxygène singulet : du dégât sur les protéines vers le développement de bio-détecteurs et générateurs(2011), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Kyoto University

Subjects
Protein Conformation, alpha-Helical, 0301 basic medicine, Cytoplasm, Proton, Motion Pictures, Biophysics, 02 engineering and technology, 03 medical and health sciences, Imaging, Three-Dimensional, Nuclear magnetic resonance, Proton transport, Molecule, fluorescent protein, Branchiostoma lanceolatum, Crystallography, Multidisciplinary, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Membrane transport protein, Chemistry, Lasers, Spectrum Analysis, Biochemistry and Molecular Biology, Bacteriorhodopsin, specific radiation damage, 021001 nanoscience & nanotechnology, Transmembrane protein, Biofysik, Time resolved crystallography, Transmembrane domain, 030104 developmental biology, in crystallo optical spectroscopy, Bacteriorhodopsins, Retinaldehyde, biology.protein, Protons, online Raman spectroscopy, 0210 nano-technology, Biokemi och molekylärbiologi
Abstract

Snapshots of bacteriorhodopsin Bacteriorhodopsin is a membrane protein that harvests the energy content from light to transport protons out of the cell against a transmembrane potential. Nango et al. used timeresolved serial femtosecond crystallography at an x-ray free electron laser to provide 13 structural snapshots of the conformational changes that occur in the nanoseconds to milliseconds after photoactivation. These changes begin at the active site, propagate toward the extracellular side of the protein, and mediate internal protonation exchanges that achieve proton transport. Science , this issue p. 1552

Published
2016
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10. Intron retention-dependent gene regulation in Cryptococcus neoformans

Author

Estelle Mogensen, Guilhem Janbon, Jungwook Hwang, Rony Barboux, Chung-Chau Hon, Pierre Lechat, Sara Gonzalez-Hilarion, Giovanni Bussotti, Kyung-Tae Lee, Damien Paulet, Jean Yves Coppée, Yong Sun Bahn, Caroline Proux, Frédérique Moyrand, Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris], Transcriptome et Epigénome (PF2), College of Life and Biotechnology [Séoul], Yonsei University, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hanyang University, This work was supported by National Research Foundation of Korea grants (2015R1A2A1A15055687) from MEST, the Strategic Initiative for Microbiomes in Agriculture and Food funded by Ministry of Agriculture, Food and Rural Affairs (916006-2) (to Y.S.B). This work was supported by a grant from ANR (2010-BLAN-1620-01 program YeastIntrons) to GJ. We thank Tae-Yup Kim and Anna Floyd for their technical assistance. We thank Cecelia Shertz Wall for editing the manuscript., ANR-10-BLAN-1620,YeastIntrons,Analyse globale de la régulation des ARN contenant des PTC par la voie du NMD et le complexe EJC-like chez des levures riches ou pauvres en introns(2010), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, MESH: Proteome / metabolism, MESH: Gene Expression, Proteome, RNA Stability, 030106 microbiology, MESH: Proteome / genetics, Gene Expression, MESH: Gene Expression Regulation, Fungal, MESH: Molecular Sequence Annotation, Article, Fungal Proteins, 03 medical and health sciences, MESH: Introns, Fungal genetics, Gene Expression Regulation, Fungal, Gene expression, MESH: Fungal Proteins / genetics, Gene, MESH: Cryptococcus neoformans / genetics, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Cryptococcus neoformans, Genetics, Regulation of gene expression, Fungal protein, Multidisciplinary, biology, MESH: Alternative Splicing, Alternative splicing, Intron, MESH: RNA Stability, Molecular Sequence Annotation, biology.organism_classification, Introns, Alternative Splicing, 030104 developmental biology, MESH: Genome, Fungal, MESH: Cryptococcus neoformans / metabolism, MESH: Fungal Proteins / metabolism, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Genome, Fungal
Abstract

The biological impact of alternative splicing is poorly understood in fungi, although recent studies have shown that these microorganisms are usually intron-rich. In this study, we re-annotated the genome of C. neoformans var. neoformans using RNA-Seq data. Comparison with C. neoformans var. grubii revealed that more than 99% of ORF-introns are in the same exact position in the two varieties whereas UTR-introns are much less evolutionary conserved. We also confirmed that alternative splicing is very common in C. neoformans, affecting nearly all expressed genes. We also observed specific regulation of alternative splicing by environmental cues in this yeast. However, alternative splicing does not appear to be an efficient method to diversify the C. neoformans proteome. Instead, our data suggest the existence of an intron retention-dependent mechanism of gene expression regulation that is not dependent on NMD. This regulatory process represents an additional layer of gene expression regulation in fungi and provides a mechanism to tune gene expression levels in response to any environmental modification.

Published
2016
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11. Transcriptional, post-transcriptional and chromatin-associated regulation of pri-miRNAs, pre-miRNAs and moRNAs

Author

Ferenc Müller, Vidar M. Steen, Jesper B. Andersen, Laure Bally-Cuif, Chirag Nepal, Marion Coolen, Boris Lenhard, Piotr Mydel, Piero Carninci, Yavor Hadzhiev, Delphine Cussigh, Biotech Research and Innovation Centre (BRIC), University of Copenhagen = Københavns Universitet (KU), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), School of Clinical and Experimental Medicine, College of Medical and Dental Science, Broegelmann Research Laboratory, Department of Clinical Science, University of Oslo (UiO), RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Institute of Clinical Sciences, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, and Commission of the European Communities

Subjects
0301 basic medicine, Ribonuclease III, Transcription, Genetic, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 05 Environmental Sciences, Embryonic Development, RNA polymerase II, Histones, 03 medical and health sciences, microRNA, Genetics, Transcriptional regulation, RNA Precursors, Animals, RNA Processing, Post-Transcriptional, Promoter Regions, Genetic, Drosha, Zebrafish, Regulation of gene expression, 08 Information And Computing Sciences, biology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Gene regulation, Chromatin and Epigenetics, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Promoter, 06 Biological Sciences, Chromatin, Cell biology, MicroRNAs, 030104 developmental biology, Histone, Gene Expression Regulation, biology.protein, RNA, Small Untranslated, RNA Polymerase II, Transcription Initiation Site, Developmental Biology
Abstract

International audience; MicroRNAs (miRNAs) play a major role in the post-transcriptional regulation of target genes, especially in development and differentiation. Our understanding about the transcriptional regulation of miRNA genes is limited by inadequate annotation of primary miRNA (pri-miRNA) transcripts. Here, we used CAGE-seq and RNA-seq to provide genome-wide identification of the pri-miRNA core promoter repertoire and its dynamic usage during zebrafish embryogenesis. We assigned pri-miRNA promoters to 152 precursor-miRNAs (pre-miRNAs), the majority of which were supported by promoter associated post-translational histone modifications (H3K4me3, H2A.Z) and RNA polymerase II (RNAPII) occupancy. We validated seven miR-9 pri-miRNAs by in situ hybridization and showed similar expression patterns as mature miR-9. In addition, processing of an alternative intronic promoter of miR-9-5 was validated by 5' RACE PCR. Developmental profiling revealed a subset of pri-miRNAs that are maternally inherited. Moreover, we show that promoter-associated H3K4me3, H2A.Z and RNAPII marks are not only present at pri-miRNA promoters but are also specifically enriched at pre-miRNAs, suggesting chromatin level regulation of pre-miRNAs. Furthermore, we demonstrated that CAGE-seq also detects 3'-end processing of pre-miRNAs on Drosha cleavage site that correlates with miRNA-offset RNAs (moRNAs) production and provides a new tool for detecting Drosha processing events and predicting pre-miRNA processing by a genome-wide assay.

Published
2016
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12. Evolutionary diversification of retinoic acid receptor ligand-binding pocket structure by molecular tinkering

Author

Romain A. Studer, Susana Alvarez, William Bourguet, Juliana Gutierrez-Mazariegos, Michael Schubert, Shigehiro Kuraku, Vincent Laudet, Angel R. de Lera, Eswar Kumar Nadendla, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Ecology and Evolution, Université de Lausanne (UNIL), Departamento de Química Orgánica, Universidate de Vigo, Genome Resource and Analysis Unit (GRAS), RIKEN Center for Developmental Biology, Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire, Molecular Zoology Team, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Universidade de Vigo, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CNRS, ENS de Lyon, UPMC (Universite Paris 06), Agence Nationale de la Recherche [ANR-2010-BLAN-1234-01, ANR-11-JSV2-002-01], MINECO (FEDER) [SAF2013-48397-R], Xunta de Galicia (Consolidacion, INBIOMED-FEDER 'Unha maneira de facer Galicia'), European Union (FP7) [BIOCAPS 316265/REGPOT-2012-2013.1], École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), RIKEN Center for Life Science Technologies, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Schubert, Michael, and Laudet, Vincent

Subjects
0301 basic medicine, Lineage (evolution), Paralogous Gene, Corrections, nuclear hormone receptor signalling, cyclostomes, 03 medical and health sciences, biology.animal, Gene duplication, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene family, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, vertebrate evolution, lcsh:Science, neoplasms, emergence of evolutionary novelty, ComputingMilieux_MISCELLANEOUS, Genetics, gene and whole genome duplication, hagfish and lamprey, Multidisciplinary, biology, Lamprey, organic chemicals, Biology (Whole Organism), Vertebrate, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, biology.organism_classification, biological factors, body regions, Retinoic acid receptor, 030104 developmental biology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, embryonic structures, lcsh:Q, Research Article, Hagfish
Abstract

Whole genome duplications (WGDs) have been classically associated with the origin of evolutionary novelties and the so-called duplication-degeneration-complementation model describes the possible fates of genes after duplication. However, how sequence divergence effectively allows functional changes between gene duplicates is still unclear. In the vertebrate lineage, two rounds of WGDs took place, giving rise to paralogous gene copies observed for many gene families. For the retinoic acid receptors (RARs), for example, which are members of the nuclear hormone receptor (NR) superfamily, a unique ancestral gene has been duplicated resulting in three vertebrate paralogues: RAR alpha, RAR beta and RAR gamma. It has previously been shown that this single ancestral RAR was neofunctionalized to give rise to a larger substrate specificity range in the RARs of extant jawed vertebrates (also called gnathostomes). To understand RAR diversification, the members of the cyclostomes (lamprey and hagfish), jawless vertebrates representing the extant sister group of gnathostomes, provide an intermediate situation and thus allow the characterization of the evolutionary steps that shaped RAR ligand-binding properties following the WGDs. In this study, we assessed the ligand-binding specificity of cyclostome RARs and found that their ligand-binding pockets resemble those of gnathostome RAR alpha and RAR beta. In contrast, none of the cyclostome receptors studied showed any RAR gamma-like specificity. Together, our results suggest that cyclostome RARs cover only a portion of the specificity repertoire of the ancestral gnathostome RARs and indicate that the establishment of ligand-binding specificity was a stepwise event. This iterative process thus provides a rare example for the diversification of receptor-ligand interactions of NRs following WGDs.

Published
2016
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13. Marmoset Serotonin 5-HT 1A Receptor Mapping with a Biased Agonist PET Probe 18 F-F13714: Comparison with an Antagonist Tracer 18 F-MPPF in Awake and Anesthetized States

Author

Chiho Takeda, Kayo Onoe, Aya Mawatari, Hirotaka Onoe, Adrian Newman-Tancredi, Luc Zimmer, Hisashi Doi, Akihiro Kawasaki, Chihiro Yokoyama, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neurolixis, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rayet, Béatrice, Centre de recherche en neurosciences de Lyon (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Fluorine Radioisotopes, Pyridines, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], Caudate nucleus, Aminopyridines, Piperazines, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Callithrix jacchus, Pharmacology (medical), Tissue Distribution, Receptor, medicine.diagnostic_test, Brain, Callithrix, Molecular Imaging, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, biased agonism, Positron emission tomography, Receptor, Serotonin, 5-HT1A, 5-HT1A receptor, MPPF, Protein Binding, Agonist, Consciousness, medicine.drug_class, Anesthesia, General, 5-hydroxytryptamine, 03 medical and health sciences, Predictive Value of Tests, medicine, Animals, Regular Research Article, Pharmacology, Binding potential, Serotonin 5-HT1 Receptor Agonists, F13714, 030104 developmental biology, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, chemistry, Positron-Emission Tomography, Serotonin, Radiopharmaceuticals, Neuroscience, 030217 neurology & neurosurgery
Abstract

Background In vivo mapping by positron emission tomography of the serotonin 1A receptors has been hindered by the lack of suitable agonist positron emission tomography probes. 18 F-labeled F13714 is a recently developed biased agonist positron emission tomography probe that preferentially targets subpopulations of serotonin 1A receptors in their " active state, " but its brain labeling pattern in nonhuman primate has not been described. In addition, a potential confound in the translatability of PET data between nonhuman animal and human arise from the use of anesthetics that may modify the binding profiles of target receptors. Methods Positron emission tomography scans were conducted in a cohort of common marmosets (n = 4) using the serotonin 1A receptor biased agonist radiotracer, 18 F-F13714, compared with a well-characterized 18 F-labeled antagonist radiotracer, 18 F-MPPF. Experiments on each animal were performed under both consciousness and isoflurane-anesthesia conditions. Results 18 F-F13714 binding distribution in marmosets by positron emission tomography differs markedly from that of the of the 18F-MPPF. Whereas 18F-MPPF showed highest binding in hippocampus and amygdala, 18F-F13714 showed highest labeling in other regions, including insular and cingulate cortex, thalamus, raphe, caudate nucleus, and putamen. The binding potential values of 18F-F13714 were about one-third of those observed with 18F-MPPF, with marked individual- and region-specific differences under isoflurane-anesthetized vs conscious conditions. Conclusions These findings highlight the importance of investigating the brain imaging of serotonin 1A receptors using agonist probes such as 18F-F13714, which may preferentially target subpopulations of serotonin 1A receptors in specific brain regions of nonhuman primate as a biased agonist.

Published
2016
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