UMMS Affiliation

Department of Pediatrics

Date

4-27-2004

Document Type

Article

Medical Subject Headings

*Cell Lineage; Electrophoresis, Agar Gel; *Gene Expression; Phylogeny; RNA, Messenger

Disciplines

Hematology | Oncology | Pediatrics

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.

Comments

Citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6508-13. Epub 2004 Apr 19. doi: 10.1073/pnas.0401136101. Link to article on publisher's website

Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/misc/authorfaq.shtml.

Related Resources

Link to article in PubMed

PubMed ID

15096607

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