A HaemAtlas: characterizing gene expression in differentiated human blood cells

Author:

Watkins Nicholas A.1,Gusnanto Arief2,de Bono Bernard3,De Subhajyoti4,Miranda-Saavedra Diego5,Hardie Debbie L.6,Angenent Will G. J.7,Attwood Antony P.7,Ellis Peter D.7,Erber Wendy8,Foad Nicola S.1,Garner Stephen F.1,Isacke Clare M.9,Jolley Jennifer1,Koch Kerstin1,Macaulay Iain C.1,Morley Sarah L.1,Rendon Augusto1,Rice Kate M.7,Taylor Niall1,Thijssen-Timmer Daphne C.10,Tijssen Marloes R.10,van der Schoot C. Ellen10,Wernisch Lorenz2,Winzer Thilo1,Dudbridge Frank2,Buckley Christopher D.6,Langford Cordelia F.7,Teichmann Sarah4,Göttgens Berthold5,Ouwehand Willem H.17

Affiliation:

1. Department of Haematology, University of Cambridge, National Health Service Blood and Transplant, Cambridge, United Kingdom;

2. Medical Research Council Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, United Kingdom;

3. European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom;

4. Structural Studies, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom;

5. Wellcome Trust/Medical Research Council Building, Cambridge, United Kingdom;

6. Division of Immunity and Infection, Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom;

7. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom;

8. Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom;

9. Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom; and

10. Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

Abstract

Abstract Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. A bioinformatics analysis of these data was performed focusing on transcription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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