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A HaemAtlas: characterizing gene expression in differentiated human blood cells.

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.

SUBMITTER: Watkins NA

PROVIDER: S-EPMC2680378 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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A HaemAtlas: characterizing gene expression in differentiated human blood cells.

Watkins Nicholas A NA Gusnanto Arief A de Bono Bernard B De Subhajyoti S Miranda-Saavedra Diego D Hardie Debbie L DL Angenent Will G J WG Attwood Antony P AP Ellis Peter D PD Erber Wendy W Foad Nicola S NS Garner Stephen F SF Isacke Clare M CM Jolley Jennifer J Koch Kerstin K Macaulay Iain C IC Morley Sarah L SL Rendon Augusto A Rice Kate M KM Taylor Niall N Thijssen-Timmer Daphne C DC Tijssen Marloes R MR van der Schoot C Ellen CE Wernisch Lorenz L Winzer Thilo T Dudbridge Frank F Buckley Christopher D CD Langford Cordelia F CF Teichmann Sarah S Göttgens Berthold B Ouwehand Willem H WH

Blood 20090219 19

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 perform ...[more]

PMID: 19228925

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Project description:UnlabelledPreeclampsia is a major obstetrical complication affecting maternal and fetal health. While it is clear that there is a substantial placental contribution to preeclampsia pathogenesis, the maternal contribution is less well characterized. We therefore performed a genome-wide transcriptome analysis to explore disease-associated changes in maternal gene expression patterns in peripheral blood mononuclear cells (PBMCs).MethodsPreeclampsia was defined as gestational hypertension, proteinuria and hyperurecimia. Total RNA was isolated from PBMCs obtained from women with uncomplicated pregnancies (n = 5) and women with preeclamptic pregnancies (n = 5). Gene expression analysis was carried out using Agilent oligonucleotide microarrays. Biological pathway analysis was undertaken using Ingenuity Pathway Analysis software. Quantitative real-time PCR (QRTPCR) was performed to validate the gene expression changes of selected genes in normotensive and preeclamptic patients (n = 12 each).ResultsWe identified a total of 368 genes that were differentially expressed in women with preeclampsia compared to normal controls with false discovery rate (FDR) controlled at 10%. In follow up experiments we further analyzed the expression levels of a number of genes that were identified as altered by the microarray data including survivin (BIRC5), caveolin (CAV1), GATA binding protein-1 (GATA1), signal tranducer and activator of transcription 1 (STAT1), E2F transcription factor-1 (E2F1), fibronectin-1 (FN1), interleukin-4 (IL-4), matrix metalloprotease-9 (MMP-9) and WAP four disulfide domain protein (WFDC-1) by QRTPCR. Additionally we performed immuno blot analysis and zymography to verify some of these candidate genes at the protein level. Computational analysis of gene function identified an anti-proliferative and altered immune function cellular phenotype in severe preeclamptic samples.ConclusionsWe have characterized the genome-wide mRNA expression changes associated with preeclampsia-specific genes in circulating maternal blood cells at the time of delivery. In addition to providing information relating to the biological basis of the preeclampsia phenotype, our data provide a number of potential biomarkers for use in the further characterization of this disease.

Dataset Information

A HaemAtlas: characterizing gene expression in differentiated human blood cells.

Publications

A HaemAtlas: characterizing gene expression in differentiated human blood cells.

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