Functional clustering and lineage markers: Insights into cellular differentiation and gene function from large-scale microarray studies of purified primary cell populations
Functional clustering and lineage markers: Insights into cellular differentiation and gene function from large-scale microarray studies of purified primary cell populations
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DOI：
10.1016/j.ygeno.2010.03.002
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发表时间：
2010-06-01
期刊：
影响因子：
4.4
通讯作者：
Freeman, Thomas C.
中科院分区：
文献类型：
--
作者：
Hume, David A.;Summers, Kim M.;Freeman, Thomas C.
显示跨多个组织和细胞群体的基因表达的非常大的微阵列数据集提供了一个关于转录网络的窗口，该网络支持生物系统之间功能活性的差异。共表达基因的簇提供谱系标记、细胞功能的候选调节物，并且通过应用关联内疚原理，提供目前未知功能的基因的候选功能。我们已经分析了包括来自造血和非造血细胞类型的纯细胞群体的数据集（http：//cnps.gnforg）。使用一种新的网络可视化和聚类方法，我们证明了有可能识别出与胚胎干细胞、间充质细胞和造血谱系特异性相关的非常紧密的表达特征。选定的例子验证了预测，基因功能可以推断的共表达。一个表达簇富集在吞噬细胞中，其与内体-溶酶体成分一起含有可能构成吞噬细胞分化的“途径”的基因。这些基因的启动子富含ETS/PU.1和MITE家族的结合位点。另一个簇与特定细胞外基质的产生相关，其中间充质来源的细胞（成纤维细胞、脂肪细胞、成骨细胞和成肌细胞）共享高水平的基因表达。我们讨论了这些数据的限制，在许多蛋白质编码基因的替代启动子具有不同的组织特异性的存在。(c)2010年爱思唯尔公司All rights reserved.
Very large microarray datasets showing gene expression across multiple tissues and cell populations provide a window on the transcriptional networks that underpin the differences in functional activity between biological systems. Clusters of co-expressed genes provide lineage markers, candidate regulators of cell function and, by applying the principle of guilt by association, candidate functions for genes of currently unknown function. We have analysed a dataset comprising pure cell populations from hemopoietic and non-hemopoietic cell types (http://biogps.gnforg). Using a novel network visualisation and clustering approach, we demonstrate that it is possible to identify very tight expression signatures associated specifically with embryonic stem cells, mesenchymal cells and hematopoietic lineages. Selected examples validate the prediction that gene function can be inferred by co-expression. One expression cluster was enriched in phagocytes, which, alongside endosome-lysosome constituents, contains genes that may make up a 'pathway' for phagocyte differentiation. Promoters of these genes are enriched for binding sites for the ETS/PU.1 and MITE families. Another cluster was associated with the production of a specific extracellular matrix, with high levels of gene expression shared by cells of mesenchymal origin (fibroblasts, adipocytes, osteoblasts and myoblasts). We discuss the limitations placed upon such data by the presence of alternative promoters with distinct tissue specificity within many protein-coding genes. (c) 2010 Elsevier Inc. All rights reserved.