Lineage Specificity of Gene Expression Patterns

Lineage Specificity of Gene Expression Patterns

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...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 17; pp. 6508 - 6513
Main Authors: Kluger, Yuval, Tuck, David P., Chang, Joseph T., Nakayama, Yasuhiro, Poddar, Ranjana, Kohya, Naohiko, Lian, Zheng, Ben Nasr, Abdelhakim, Halaban, H. Ruth, Krause, Diane S., Zhang, Xueqing, Newburger, Peter E., Weissman, Sherman M.
Format: Journal Article
Language:English
Published: United States National Academy of Sciences 27-04-2004
National Acad Sciences
Subjects:
B lymphocytes
Biological Sciences
Biology
Cell Lineage
Cell lines
Cells
Electrophoresis, Agar Gel
Gene Expression
Genes
Genetic variation
Genetic vectors
Neutrophils
Phylogeny
Principal components analysis
RNA, Messenger - genetics
Stem cells
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Summary: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 implicity contained information about developmental relationships among cell types.
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Abbreviations: PCA, principal component analysis; KEGG, Kyoto Encyclopedia of Genes and Genomes.
To whom correspondence should be addressed at: Department of Genetics, Yale University School of Medicine, TAC S-319, 300 Cedar Street, New Haven, CT 06510. E-mail: sherman.weissman@yale.edu.
Contributed by Sherman M. Weissman, February 17, 2004
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0401136101