RESUMEN
Follicular dendritic cells (FDC) are an important subset of stromal cells within the germinal centres of lymphoid tissues. They are specialized to trap and retain antigen-containing immune complexes on their surfaces to promote B-cell maturation and immunoglobulin isotype class-switching. However, little is known of the cell types from which FDC originate. To address fundamental questions associated with the relationships between FDC and other cell populations, we took advantage of the growing body of publicly available data for transcriptome analysis. We obtained a large number of gene expression data files from a range of different primary mouse cells and cell lines and subjected these data to network-based cluster analysis using BiolayoutExpress(3D) . Genes with related function clustered together in distinct regions of the graph and enabled the identification of transcriptional networks that underpin the functional activity of distinct cell populations. Several gene clusters were identified that were selectively expressed by cells of mesenchymal lineage and contained classic mesenchymal cell markers and extracellular matrix genes including various collagens, Acta2, Bgn, Fbn1 and Twist1. Our analysis showed that FDC also express highly many of these mesenchyme-associated genes. Promoter analysis of the genes comprising the mesenchymal clusters identified several regulatory motifs that are binding sites for candidate transcription factors previously known to be candidate regulators of mesenchyme-specific genes. Together, these data suggest FDC are a specialized mesenchymal cell population within the germinal centres of lymphoid tissues.
Asunto(s)
Células Dendríticas Foliculares/metabolismo , Matriz Extracelular/genética , Mesodermo/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Animales , Biomarcadores , Línea Celular , Humanos , Metaanálisis como Asunto , RatonesRESUMEN
In order to address fundamental questions associated with the relationships between mononuclear phagocytes and other myeloid and lymphoid cell populations, we have taken advantage of the growing body of expression data available in the public domain. We collated a large number of published expression studies on mouse haemopoietic cell lineages comprising 304 cell samples from 29 independent experiments performed on a single microarray platform (Affymetrix MOE430-2). The data were subjected to network-based cluster analysis using Biolayout Express(3D). Genes with related function clustered together in distinct regions of the graph reaffirming many known associations between gene expression and role in specific pathways and defining most major cell types of the immune system. Promoters of genes within individual clusters were distinguished by over-representation of regulatory motifs recognised by specific transcription factors. However, these data indicate that commonly used myeloid subpopulation markers, such as CD11c (Itgax), do not correlate with expression of other genes, and further bring into question their use in defining myeloid cell lineage, activation (M1 vs. M2) and antigen-presenting cell function. In particular, there were few mRNA markers that clearly distinguished classical dendritic cells (DC) from macrophages, other than low expression of genes required for phagocytic activity. Bone marrow-derived DC, grown in GM-CSF, were clearly identified as phagocytes and distinguished from isolated lymphoid tissue DC. Thus, through pooling datasets from public data and examining the gene expression clusters within, we can learn a great deal about the transcriptional networks that underpin the differences in functional activities between cell populations of the immune system.