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
Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6508-13. doi: 10.1073/pnas.0401136101. Epub 2004 Apr 19.
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.
造血系统作为理解细胞谱系选择和特化一般方面的模型具有许多优势。我们使用寡核苷酸微阵列比较了多种纯化的造血细胞群体的基因表达模式，这些群体包括中性粒细胞、单核细胞、巨噬细胞、静息B淋巴细胞、中心细胞性B淋巴细胞、中心母细胞性B淋巴细胞、树突状细胞和造血干细胞。其中一些细胞在静息和刺激条件下均进行了研究。我们研究了源自功能途径的Biocarta数据库的基因子集的集体行为、基于基因本体数据库将基因手动分类为广泛功能类别的分组以及京都基因与基因组百科全书数据库中的代谢途径。主成分分析揭示了在涉及大多数所检查子集的细胞谱系之间，基因表达相对水平存在显著普遍差异。这些结果表明，这些细胞中的许多过程在不同谱系中表现不同。谱系间的许多差异可由最初的几个主成分体现。发现主成分双标图能方便地直观展示子集中各种基因在谱系区分中的贡献。此外，通过将从系统发育学借用的树构建方法应用于分化细胞和干细胞的表达数据，我们重建了一个关系树，它类似于已确立的造血谱系发育程序。因此，mRNA表达数据隐含地包含了有关细胞类型之间发育关系的信息。
