Lineage specificity of gene expression patterns

Abstract

The hematopoietic system offers many advantages as a model for understanding general aspects of lineage choice and specification. Using oligonucleotide microarrays, we compared gene expression patterns of multiple purified hematopoietic cell populations, including neutrophils, monocytes, macrophages, resting, centrocytic, and centroblastic B lymphocytes, dendritic cells, and hematopoietic stem cells. Some of these cells were studied under both resting and stimulated conditions. We studied the collective behavior of subsets of genes derived from the Biocarta database of functional pathways, hand-tuned groupings of genes into broad functional categories based on the Gene Ontology database, and the metabolic pathways in the Kyoto Encyclopedia of Genes and Genomes database. Principal component analysis revealed strikingly pervasive differences in relative levels of gene expression among cell lineages that involve most of the subsets examined. These results indicate that many processes in these cells behave differently in different lineages. Much of the variation among lineages was captured by the first few principal components. Principal components biplots were found to provide a convenient visual display of the contributions of the various genes within the subsets in lineage discrimination. Moreover, by applying tree-constructing methodologies borrowed from phylogenetics to the expression data from differentiated cells and stem cells, we reconstructed a tree of relationships that resembled the established hematopoietic program of lineage development. Thus, the mRNA expression data implicitly contained information about developmental relationships among cell types.

Memory T cells have gene expression patterns intermediate between naïve and effector

“…A recent report (8) (2). Furthermore, MEM cells may go back to this intermediary state subsequent to activation to become EFFEs.…”

“…In the same spirit as ref. 8, we performed a phylogenetic analysis, considering the genes to be either expressed, underexpressed, or off. These three categories of expression are considered ordinal.…”

“…Recently, microarray analysis of hematopoietic cells demonstrated that gene expression data implicitly contain information about developmental relationships amongst cell types and lineage discrimination (8). Hence, we hypothesized that systematic comparisons of the gene expression patterns of NAI, EFFE, and MEM T cells might also shed light on the issue of linear versus parallel differentiation of T cells.…”

Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

“…Two-way (antibodies against specimens) hierarchical clustering and principal component analysis were applied to group the samples of the study population based on the similarity of their anti-Candida wall antibody expression profiles (53,54). Anti-Candida wall IgG antibody levels were normalized by median centering antibodies for each specimen and then by median centering each antibody across all specimens.…”

Harnessing the developmental potential of nucellar cells: barriers and opportunities

“…The zygote and the early embryonic stem cells (ESCs) are totipotent; by contrast, the germline stem cells are unipotent, giving rise to either male or female gametes. The haematopoietic stem cells are the bestcharacterized pluripotent stem cells; located in the bone marrow of mice and humans, they generate the dozen or more cell types of the blood [40].…”