title: Transcriptional diversity during lineage commitment of human blood progenitors.
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.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.|Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Myrto
authors.initials: M
authors.lastname: Kostadima
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands.
authors.forename: Joost H A
authors.initials: JHA
authors.lastname: Martens
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Canu
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Sara P
authors.initials: SP
authors.lastname: Garcia
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Ernest
authors.initials: E
authors.lastname: Turro
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Downes
authors.affiliation: Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macaulay
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Ewa
authors.initials: E
authors.lastname: Bielczyk-Maczynska
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Sophia
authors.initials: S
authors.lastname: Coe
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Samantha
authors.initials: S
authors.lastname: Farrow
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Pawan
authors.initials: P
authors.lastname: Poudel
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Frances
authors.initials: F
authors.lastname: Burden
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Sjoert B G
authors.initials: SBG
authors.lastname: Jansen
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.|Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: William J
authors.initials: WJ
authors.lastname: Astle
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Antony
authors.initials: A
authors.lastname: Attwood
authors.affiliation: Department of Haematology, University College London Cancer Institute, London, United Kingdom.|The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom.
authors.forename: Tadbir
authors.initials: T
authors.lastname: Bariana
authors.affiliation: CHIME Institute, University College London, Archway Campus, London, United Kingdom.|Auckland Bioengineering Institute, University of Auckland, New Zealand.
authors.forename: Bernard
authors.initials: B
authors.lastname: de Bono
authors.affiliation: Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Breschi
authors.affiliation: Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom.|Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom.
authors.forename: John C
authors.initials: JC
authors.lastname: Chambers
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Bridge
authors.initials: B
authors.lastname: Consortium
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Fizzah A
authors.initials: FA
authors.lastname: Choudry
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Clarke
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Coupland
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: van der Ent
authors.affiliation: Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Erber
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Joop H
authors.initials: JH
authors.lastname: Jansen
authors.affiliation: Assistance Publique-Hopitaux de Paris, Institut National de la Santé et de la Recherche Médicale U1009, Villejuif, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Favier
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Fenech
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Foad
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Freson
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: van Geet
authors.affiliation: The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Gomez
authors.affiliation: Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain.
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigo
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hampshire
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.|Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Kelly
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands.
authors.forename: Hindrik H D
authors.initials: HHD
authors.lastname: Kerstens
authors.affiliation: Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom.|Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom.
authors.forename: Jaspal S
authors.initials: JS
authors.lastname: Kooner
authors.affiliation: Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Laffan
authors.affiliation: Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Lentaigne
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Labalette
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.|Department of Twin Research & Genetic Epidemiology, Genetics & Molecular Medicine Division, St Thomas' Hospital, King's College, London, United Kingdom.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Martin
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Meacham
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mumford
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Nürnberg
authors.affiliation: Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Palumbo
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Bert A
authors.initials: BA
authors.lastname: van der Reijden
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Richardson
authors.affiliation: Department of Oncology, Addenbrooke's Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom.|Cancer Research United Kingdom, Cambridge Institute, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sammut
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Greg
authors.initials: G
authors.lastname: Slodkowicz
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Asif U
authors.initials: AU
authors.lastname: Tamuri
authors.affiliation: NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Louella
authors.initials: L
authors.lastname: Vasquez
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Katrin
authors.initials: K
authors.lastname: Voss
authors.affiliation: NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Watt
authors.affiliation: School of Clinical Sciences, University of Bristol, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Westbury
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Remco
authors.initials: R
authors.lastname: Loos
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Goldman
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.|Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Heidelberg, Germany.|Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Bertone
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Read
authors.affiliation: Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Richardson
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Cvejic
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.|Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Mattia
authors.initials: M
authors.lastname: Frontini
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.|Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Augusto
authors.initials: A
authors.lastname: Rendon
mesh_terms: D017398:Alternative Splicing; D019070:Cell Lineage / Q000235:genetics*; D014644:Genetic Variation; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D034061:Thrombopoiesis / Q000235:genetics; D059467:Transcriptome
chemical_list: D051839:NFI Transcription Factors; C110754:NFIB protein, human; D016601:RNA-Binding Proteins