1. A high-resolution anatomical atlas of the transcriptome in the mouse embryo
- Author
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Graciana Diez-Roux, Sandro Banfi, Marc Sultan, Lars Geffers, Santosh Anand, David Rozado, Alon Magen, Elena Canidio, Massimiliano Pagani, Ivana Peluso, Nathalie Lin-Marq, Muriel Koch, Marchesa Bilio, Immacolata Cantiello, Roberta Verde, Cristian De Masi, Salvatore A Bianchi, Juliette Cicchini, Elodie Perroud, Shprese Mehmeti, Emilie Dagand, Sabine Schrinner, Asja Nürnberger, Katja Schmidt, Katja Metz, Christina Zwingmann, Norbert Brieske, Cindy Springer, Ana Martinez Hernandez, Sarah Herzog, Frauke Grabbe, Cornelia Sieverding, Barbara Fischer, Kathrin Schrader, Maren Brockmeyer, Sarah Dettmer, Christin Helbig, Violaine Alunni, Marie-Annick Battaini, Carole Mura, Charlotte N Henrichsen, Raquel Garcia-Lopez, Diego Echevarria, Eduardo Puelles, Elena Garcia-Calero, Stefan Kruse, Markus Uhr, Christine Kauck, Guangjie Feng, Nestor Milyaev, Chuang Kee Ong, Lalit Kumar, MeiSze Lam, Colin A Semple, Attila Gyenesei, Stefan Mundlos, Uwe Radelof, Hans Lehrach, Paolo Sarmientos, Alexandre Reymond, Duncan R Davidson, Pascal Dollé, Stylianos E Antonarakis, Marie-Laure Yaspo, Salvador Martinez, Richard A Baldock, Gregor Eichele, Andrea Ballabio, Telethon Institute for Genetics and Medicine, Telethon Institute, Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, Genes and Behavior Department [Göttingen], Max Planck Institute for Biophysical Chemistry (MPI-BPC), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Primm, Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Institut Clinique de la Souris (ICS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Experimental Embryology Lab, Universidad Miguel Hernández [Elche] (UMH)-Instituto de Neurociencias, ORGARAT, Human Genetics Unit, Medical Research Council, Deutsches Ressourcenzentrum für Genomforschung (RZPD), Deutsches Ressourcenzentrum für Genomforschung, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Medical Genetics, Università degli studi di Napoli Federico II, Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital [Houston, USA], This work was supported by the EC VI Framework Programme contract number LSHG-CT-2004-512003. The authors also acknowledge the support of: the Italian Telethon Foundation (AB, SB, and GD-R), the Swiss National Science Foundation (AR and SEA), the Max Planck Society (GE, M-LY, HL), MRC (RB, DD), Association pour la Recherche sur le Cancer (PD), and Ingenio 2010 MEC-CONSOLIDER CSD2007-00023, DIGESIC-MEC BFU2008-00588, CIBERSAM/ISCIII (SM)., Université de Genève = University of Geneva (UNIGE), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), University of Naples Federico II = Università degli studi di Napoli Federico II, Autard, Delphine, Diez Roux, G, Banfi, Sandro, Sultan, M, Geffers, L, Anand, S, Rozado, D, Magen, A, Canidio, E, Pagani, M, Peluso, I, Lin Marq, N, Koch, M, Bilio, M, Cantiello, I, Verde, R, De Masi, C, Bianchi, Sa, Cicchini, J, Perroud, E, Mehmeti, S, Dagand, E, Schrinner, S, Nürnberger, A, Schmidt, K, Metz, K, Zwingmann, C, Brieske, N, Springer, C, Martinez Hernandez, A, Herzog, S, Grabbe, F, Sieverding, C, Fischer, B, Schrader, K, Bürsing, M, Schubert, S, Helbig, C, Alunni, V, Battaini, Ma, Mura, C, Henrichsen, Cn, Garcia Lopez, R, Echevarria, D, Puelles, E, Garcia Calero, E, Kruse, S, Uhr, M, Kauck, C, Feng, G, Milyaev, N, Ong, Ck, Kumar, L, Lam, M, Semple, Ca, Gyenesei, A, Mundlos, S, Radelof, U, Lehrach, H, Sarmientos, P, Reymond, A, Davidson, Dr, Dollé, P, Antonarakis, Se, Yaspo, Ml, Martinez, M, Baldock, Ra, Eichele, G, Ballabio, A., Banfi, S, Reymond, R, Martinez, S, Ballabio, Andrea, and Reymond, Alexandre
- Subjects
Transcriptome ,Mice ,0302 clinical medicine ,Databases, Genetic ,Gene expression ,Animals ,Atlases as Topic ,Embryo, Mammalian ,Gene Expression Profiling ,Internet ,Mice/anatomy & histology ,Mice/embryology ,Mice, Inbred C57BL ,Organ Specificity ,ddc:576.5 ,MESH: Animals ,Biology (General) ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,MESH: Databases, Genetic ,MESH: Organ Specificity ,Genetics ,0303 health sciences ,Agricultural and Biological Sciences(all) ,General Neuroscience ,Wnt signaling pathway ,Genetics and Genomics/Gene Expression ,Genome project ,MESH: Internet ,General Agricultural and Biological Sciences ,Research Article ,Genetics and Genomics/Animal Genetics ,QH301-705.5 ,Neuroscience(all) ,education ,MESH: Atlases as Topic ,In situ hybridization ,Computational biology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,MESH: Gene Expression Profiling ,Mice/anatomy & histology/embryology/genetics ,MESH: Mice, Inbred C57BL ,Immunology and Microbiology(all) ,microRNA ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,Gene ,MESH: Mice ,030304 developmental biology ,General Immunology and Microbiology ,Biochemistry, Genetics and Molecular Biology(all) ,MESH: Embryo, Mammalian ,Gene expression profiling ,Genetics and Genomics/Genome Projects ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The manuscript describes the “digital transcriptome atlas” of the developing mouse embryo, a powerful resource to determine co-expression of genes, to identify cell populations and lineages and to identify functional associations between genes relevant to development and disease., Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease., Author Summary In situ hybridization (ISH) can be used to visualize gene expression in cells and tissues in their native context. High-throughput ISH using nonradioactive RNA probes allowed the Eurexpress consortium to generate a comprehensive, interactive, and freely accessible digital gene expression atlas, the Eurexpress transcriptome atlas (http://www.eurexpress.org), of the E14.5 mouse embryo. Expression data for over 15,000 genes were annotated for hundreds of anatomical structures, thus allowing us to systematically identify tissue-specific and tissue-overlapping gene networks. We illustrate the value of the Eurexpress atlas by finding novel regional subdivisions in the developing brain. We also use the transcriptome atlas to allocate specific components of the complex Wnt signaling pathway to kidney development, and we identify regionally expressed genes in liver that may be markers of hematopoietic stem cell differentiation.
- Published
- 2011
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