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Hematopoiesis
Cell type-specific novel long non-coding RNA and circular RNA in the BLUEPRINT hematopoietic transcriptomes atlas
Luigi Grassi,1,2,3*° Osagie G. Izuogu,4* Natasha A.N. Jorge,5 Denis Seyres,1,2,3 Mariona Bustamante,6,7,8 Frances Burden,1,2,3 Samantha Farrow,1,2,3
Neda Farahi,9 Fergal J. Martin,4 Adam Frankish,4 Jonathan M. Mudge,4 Myrto Kostadima,1,2,4 Romina Petersen,1,2 John J. Lambourne,1,2
Sophia Rowlston,1,2 Enca Martin-Rendon,10,11 Laura Clarke,4
Kate Downes,1,2,3 Xavier Estivill,12 Paul Flicek,4 Joost H.A. Martens,13 Marie-Laure Yaspo,14 Hendrik G. Stunnenberg,13 Willem H. Ouwehand,1,2,3,15,16 Fabio Passetti,5,17 Ernest Turro1,2,3,18 and Mattia Frontini1,2,16,19
1Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 2National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK; 3National Institute for Health Research BioResource, Rare Diseases, Cambridge University Hospitals, Cambridge, UK; 4European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK; 5Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; 6ISGlobal, Institute for Global Health, Barcelona, Spain; 7Center for Genomic Regulation (CRG), Barcelona, Spain; 8Universitat Pompeu Fabra, Barcelona, Spain; 9Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK; 10R&D Division, National Health Service (NHS)-Blood and Transplant, Oxford Centre, Oxford, UK; 11Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; 12Genes and Disease Research Group, Genetics and Genomics Program, Sidra Research Department, Sidra Medicine, Doha, Qatar; 13Radboud University, Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands; 14Max Planck Institute for Molecular Genetics, Berlin, Germany; 15Department of Human Genetics, the Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK; 16British Heart Foundation Centre of Excellence, Cambridge Biomedical Campus, Cambridge, UK; 17Laboratory of Gene Expression Regulation, Carlos Chagas Institute, Fundação Oswaldo Cruz, Curitiba, Brazil; 18Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge, UK and 19Institute of Biomedical & Clinical Science, College of Medicine and Health, University of Exeter Medical School, Exeter, UK
*LG and OGI contributed equally as co-first authors.
°Current affiliation: Biopharmaceutical Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
ABSTRACT
Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microar- rays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analyzed the BLUEPRINT consortium RNA-sequencing data for mature hematopoietic cell types. The data comprised 90 total RNA-sequencing samples, each composed of one of 27 cell types, and 32 small RNA-sequencing samples, each composed of one of 11 cell types. We estimated gene and isoform expression levels for each cell type using existing annotations from Ensembl. We then used guided transcriptome assembly to discover unannotated transcripts. We identified hundreds of novel non-coding RNA genes and showed that the majority have cell type-dependent expression. We also characterized the expression of circular RNA and found that these are also cell type-specific. These analy- ses refine the active transcriptional landscape of mature hematopoietic cells, highlight abundant genes and transcriptional isoforms for each blood cell type, and provide a valuable resource for researchers of hematologic devel- opment and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/.
Ferrata Storti Foundation
Haematologica 2021 Volume 106(10):2613-2623
Correspondence:
MATTIA FRONTINI
mf471@cam.ac.uk
ERNEST TURRO
et341@cam.ac.uk
Received: September 23, 2019. Accepted: July 16, 2020. Pre-published: July 23, 2020.
https://doi.org/10.3324/haematol.2019.238147 ©2021 Ferrata Storti Foundation
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