Year: 2014
Type: article
Abstract: Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.
Source: Science
Authors: Lu Chen, Myrto Kostadima, Joost H. A. Martens, Giovanni Canu, Sara P. Garcia, Ernest Turro, Kate Downes, Iain C. Macaulay, Ewa Bielczyk-Maczynska, Sophia Coe, Samantha Farrow, Pawan Poudel, Frances Burden, Sjoert B. G. Jansen, William J. Astle, Antony Attwood, Tadbir Bariana, Bernard de Bono, Alessandra Breschi, John C. Chambers, Fizzah A. Choudry, Laura Clarke, Paul Coupland, Martijn van der Ent, Wendy N. Erber, Joop H. Jansen, Rémi Favier, Matthew E. Fenech, Nicola Foad, Kathleen Freson, Chris van Geet, Keith Gomez, Roderic Guigo, Daniel Hampshire, Anne M. Kelly, Hindrik H. D. Kerstens, Jaspal S. Kooner, Michael Laffan, Claire Lentaigne, Charlotte Labalette, Tiphaine Martin, Stuart Meacham, Andrew Mumford, Sylvia T. Nürnberg, Emilio Palumbo, Bert A. van der Reijden, David Richardson, Stephen J. Sammut, Greg Slodkowicz, Asif U. Tamuri, Louella Vasquez, Katrin Voss, Stephen Watt, Sarah Westbury, Paul Flicek, Remco Loos, Nick Goldman, Paul Bertone, Randy J. Read, Sylvia Richardson, Ana Cvejic, Nicole Soranzo, Willem H. Ouwehand, Hendrik G. Stunnenberg, Mattia Frontini, Augusto Rendon
Institutions: National Health Service, NHS Blood and Transplant, University of Cambridge, Wellcome Sanger Institute, European Bioinformatics Institute, Radboud University Nijmegen, MRC Biostatistics Unit, Medical Research Council, Royal Free London NHS Foundation Trust, The Royal Free Hospital, University College London, University of Auckland, Universitat Pompeu Fabra, Centre for Genomic Regulation, Imperial College Healthcare NHS Trust, Ealing Hospital NHS Trust, The University of Western Australia, Radboud University Medical Center, Inserm, Assistance Publique – Hôpitaux de Paris, University of East Anglia, KU Leuven, Cambridge University Hospitals NHS Foundation Trust, Imperial College London, St Thomas' Hospital, King's College London, University of Bristol, Cancer Research UK, Addenbrooke's Hospital, Wellcome/MRC Cambridge Stem Cell Institute, European Molecular Biology Laboratory, European Molecular Biology Laboratory
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Ensembl, G1349290491, G2107972360, G2325242462, G2401487772, A BLUEPRINT of Haematopoietic Epigenomes, Epigenetics towards systems biology, NIHR Senior Investigator Award, Megakarocyte and Platelet Biology and Genomics, G4321129689, Pathophysiological characterization of megakaryopoiesis and platelet production: omics for thrombocytopenia and functional studies., G4612446324, Protein crystallography: development of new methods, and application to the study of pathogenesis., The UK Blood Services Common Controls DNA Collection., Cellular Medicine at the Cambridge Institute for Medical Research., G4931427633, G4978210123, G5257833011, G5725558014, G5983201483, G6564977220, Predicting plaque rupture using invasive imaging and biomechanical modelling, G7642076992, G7658546326, NIHR Senior Investigator Award, The UK Blood Services Common Controls DNA Collection., G84888450, G8491121283, Premature cardiovascular disease and platelet quantitative traits: identification and functional characterisation of novel high-penetrance mutations and rare alleles, G8538723892, G856282705, G8678334142, Protein crystallography: development of new methods, and application to the study of pathogenesis., G969978795
OpenAlex ID: W2005806113