Suchergebnisse

Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade. ; We acknowledge all participants that have attended and contributed to LifeTime meetings and workshops through many presentations and discussions. We thank J. Richers for artwork and A. Sonsala, A. Tschernycheff and C. Lozach for administrative support. LifeTime has received funding from the European Union's Horizon 2020 research and innovation framework programme under grant agreement 820431. ; Peer Reviewed ; "Article signat per 52 autors/es: Nikolaus Rajewsky, Geneviève Almouzni, Stanislaw A. Gorski, Stein Aerts, Ido Amit, Michela G. Bertero, Christoph Bock, Annelien L. Bredenoord, Giacomo Cavalli, Susanna Chiocca, Hans Clevers, Bart De Strooper, Angelika Eggert, Jan Ellenberg, Xosé M. Fernández, Marek Figlerowicz, Susan M. Gasser, Norbert Hubner, Jørgen Kjems, Jürgen A. Knoblich, Grietje Krabbe, Peter Lichter, Sten Linnarsson, Jean-Christophe Marine, John C. Marioni, Marc A. Marti-Renom, Mihai G. Netea, Dörthe Nickel, Marcelo Nollmann, Halina R. Novak, Helen Parkinson, Stefano Piccolo, Inês Pinheiro, Ana Pombo, Christian Popp, Wolf Reik, Sergio Roman-Roman, Philip Rosenstiel, Joachim L. Schultze, Oliver Stegle, Amos Tanay, Giuseppe Testa, Dimitris Thanos, Fabian J. Theis, Maria-Elena Torres-Padilla, Alfonso Valencia, Céline Vallot, Alexander van Oudenaarden, Marie Vidal, Thierry Voet & LifeTime Community Working Groups" ; Postprint (published version)

The great capability of insects to adapt to new environments promoted their extraordinary diversification, resulting in the group of Metazoa with the largest number of species distributed worldwide. To understand this enormous diversity, it is essential to investigate lineages that would allow the reconstruction of the early events in the evolution of insects. However, research on insect ecology, physiology, development and evolution has mostly focused on few well-established model species. The key phylogenetic position of mayflies within Paleoptera as the sister group of the rest of winged insects and life history traits of mayflies make them an essential order to understand insect evolution. Here, we describe the establishment of a continuous culture system of the mayfly Cloeon dipterum and a series of experimental protocols and omics resources that allow the study of its development and its great regenerative capability. Thus, the establishment of Cloeon as an experimental platform paves the way to understand genomic and morphogenetic events that occurred at the origin of winged insects. ; This project has been funded by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement 657732 to IA, Grant BFU2015-66040-P to FC and institutional Grant MDM-2016-0687 (MINECO, Spain). ; Peer reviewed

The evolution of winged insects revolutionized terrestrial ecosystems and led to the largest animal radiation on Earth. However, we still have an incomplete picture of the genomic changes that underlay this diversification. Mayflies, as one of the sister groups of all other winged insects, are key to understanding this radiation. Here, we describe the genome of the mayfly Cloeon dipterum and its gene expression throughout its aquatic and aerial life cycle and specific organs. We discover an expansion of odorant-binding-protein genes, some expressed specifically in breathing gills of aquatic nymphs, suggesting a novel sensory role for this organ. In contrast, flying adults use an enlarged opsin set in a sexually dimorphic manner, with some expressed only in males. Finally, we identify a set of wing-associated genes deeply conserved in the pterygote insects and find transcriptomic similarities between gills and wings, suggesting a common genetic program. Globally, this comprehensive genomic and transcriptomic study uncovers the genetic basis of key evolutionary adaptations in mayflies and winged insects. ; This project was mainly funded by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement 657732 to I.A., Grant BFU2015-66040-P to F.Ca., institutional Grant MDM-2016-0687 (MINECO, Spain). Additional funding was provided by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (ERC-StG-LS2-637591 to M.I.), the Spanish Ministerio de Ciencia (BFU2017-89201-P to M.I., RYC-2016-20089 and PGC2018-099392-A-I00 to I.M.). ; Peer reviewed