BloodExpress: a database of gene expression in mouse haematopoiesis

Abstract

Haematopoiesis is the process whereby blood stem cells give rise to at least fourteen functionally distinct mature cell types, and represents the best characterized mammalian adult stem cell system. Here we introduce the BloodExpress database, the first public resource integrating mouse blood cell expression profiles. BloodExpress enables the searching of data from individual studies in a single database accessible through a user-friendly web interface. Microarray datasets have been processed uniformly to allow their comparison on the BloodExpress platform. BloodExpress covers the majority of murine blood cell types, including both progenitors and terminally differentiated cells. This allows for the identification of dynamic changes in gene expression as cells differentiate down the well-defined haematopoietic hierarchy. A gene-centric interface returns haematopoietic expression patterns together with functional annotation and a list of other genes with similar expression patterns. A cell type-centric interface allows the identification of genes expressed at specific points of blood development, with the additional and useful capability of filtering by specific gene functional categories. BloodExpress thus constitutes a platform for the discovery of novel gene functions across the haematopoietic tree. BloodExpress is freely accessible at http://hscl.cimr.cam.ac.uk/bloodexpress/.

Figure 1.

Overview of adult haematopoiesis in the mouse. The classic scheme of haematopoiesis features a tree that splits into the myeloid and lymphoid lineages. The progressive restriction of developmental fates is carried out by lineage-specific transcription factors that control lineage-specific expression profiles. Of note, the previously recognized distinction between the myeloid and lymphoid lineages has recently been disputed by the finding that T-cells precursors retain the ability to ultimately give rise to macrophages (31,32). The haemangioblast is a multipotent cell and a common precursor to both haematopoietic and endothelial cells (33). The haemangioblast has been isolated from gastrulating mouse (34) and zebrafish (35) embryos as mesodermal subpopulations, although their in vivo functionality awaits demonstration. Abbreviations—Progenitors: LT-HSC (long-term haematopoietic stem cell), ST-HSC (short-term haematopoietic stem cell), LMPP (lymphoid primed multipotent progenitor); Lymphoid: CLP (common lymphoid progenitor), CTNKP (common T and natural killer progenitor), DN-x (double negative ‘x’), DP_L (double positive large), DP_S (double positive small); Myeloid: CMP (common myeloid progenitor), MEP (megakaryocyte and erythrocyte progenitor), BFU-E (blast-forming unit erythrocyte), CFU-E (colony-forming unit erythrocyte), MK-P (megakaryocyte progenitor), CFU-Mc (colony-forming unit mast cell), CFU-Eo (colony-forming unit eosinophil), CFU-Ba (colony-forming unit basophil), GMP (granulocyte and macrophage progenitor), CFU-G (colony-forming unit granulocyte), CFU-M (colony-forming unit macrophage); Dendritic: CDP (common dendritic progenitor). The coloured cell types are those included in BloodExpress.

Figure 2.

Snapshot of the gene-centric SEARCH::genes web interface. The user can search a gene's expression pattern by entering its MGI or ENSEMBL id, or by specifying a keyword that is searched against a list of gene names and gene descriptions before a list of candidates is returned to the user. The user can also specify a similarity threshold to retrieve genes with similar expression patterns.

Figure 3.

Snapshot of the cell type-centric SEARCH::cells web interface. The user can select a cell type to return a list of genes expressed therein. Queries can be refined further by excluding those genes that are expressed in the second list of cell types. The resulting gene lists can be filtered further by considering only predicted transcription factors, or genes with specific ontology terms.