Expression quantitative trait loci are highly sensitive to cellular differentiation state.
Expression quantitative trait loci are highly sensitive to cellular differentiation state.
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DOI：
10.1371/journal.pgen.1000692
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发表时间：
2009-10
期刊：
影响因子：
4.5
通讯作者：
de Haan G
中科院分区：
文献类型：
--
作者：
Gerrits A;Li Y;Tesson BM;Bystrykh LV;Weersing E;Ausema A;Dontje B;Wang X;Breitling R;Jansen RC;de Haan G
遗传基因组是一种将基因表达变异映射到表达定量性状的局部性（EQTL）我们分析了不同细胞分化状态的EQTL鲁棒性/灵敏度。 （365）在所有四种细胞类型中一直活跃的“静态” eqtl，我们发现“动态” eqtl的数量更大（1,283）显示了这些细胞类型的依赖性。在茎，祖细胞，红细胞和髓样细胞中更有可能活跃。基因。我们没有发现靶基因在不同细胞类型中受到不同eqtl的证据，这表明功能调节网络中的大规模变化很少见。因此，正在研究的细胞种群。尽可能全面地构建功能调节关系的图片。
血细胞从多能造血干细胞到专门的血细胞的发展是通过触发器仍然未知的基因表达的急剧变化来实现的。基因表达调节剂（EQTL）。从大量的遗传学不同但相关的小鼠菌株收集的血液细胞类型，我们发现，大量的eqtl（365）对基因表达具有一致的“静态”调节作用，但发现了更大的数量对细胞阶段非常敏感。 EQTL对细胞期的敏感性在很大程度上与靶基因的基因表达变化有关。细胞类型。
Genetical genomics is a strategy for mapping gene expression variation to expression quantitative trait loci (eQTLs). We performed a genetical genomics experiment in four functionally distinct but developmentally closely related hematopoietic cell populations isolated from the BXD panel of recombinant inbred mouse strains. This analysis allowed us to analyze eQTL robustness/sensitivity across different cellular differentiation states. Although we identified a large number (365) of “static” eQTLs that were consistently active in all four cell types, we found a much larger number (1,283) of “dynamic” eQTLs showing cell-type–dependence. Of these, 140, 45, 531, and 295 were preferentially active in stem, progenitor, erythroid, and myeloid cells, respectively. A detailed investigation of those dynamic eQTLs showed that in many cases the eQTL specificity was associated with expression changes in the target gene. We found no evidence for target genes that were regulated by distinct eQTLs in different cell types, suggesting that large-scale changes within functional regulatory networks are uncommon. Our results demonstrate that heritable differences in gene expression are highly sensitive to the developmental stage of the cell population under study. Therefore, future genetical genomics studies should aim at studying multiple well-defined and highly purified cell types in order to construct as comprehensive a picture of the changing functional regulatory relationships as possible. Blood cell development from multipotent hematopoietic stem cells to specialized blood cells is accompanied by drastic changes in gene expression for which the triggers remain mostly unknown. Genetical genomics is an approach linking natural genetic variation to gene expression variation, thereby allowing the identification of genomic loci containing gene expression modulators (eQTLs). In this paper, we used a genetical genomics approach to analyze gene expression across four developmentally close blood cell types collected from a large number of genetically different but related mouse strains. We found that, while a significant number of eQTLs (365) had a consistent “static” regulatory effect on gene expression, an even larger number were found to be very sensitive to cell stage. As many as 1,283 eQTLs exhibited a “dynamic” behavior across cell types. By looking more closely at these dynamic eQTLs, we show that the sensitivity of eQTLs to cell stage is largely associated with gene expression changes in target genes. These results stress the importance of studying gene expression variation in well-defined cell populations. Only such studies will be able to reveal the important differences in gene regulation between different cell types.
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影响因子：
3.7
作者：
Alberts, Rudi;Terpstra, Peter;Li, Yang;Breitling, Rainer;Nap, Jan-Peter;Jansen, Ritsert C.
通讯作者：
Jansen, Ritsert C.
影响因子：
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作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
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作者：
Goering, Harald H. H.;Curran, Joanne E.;Blangero, John
通讯作者：
Blangero, John
影响因子：
30.8
作者：
Bystrykh, L;Weersing, E;de Haan, G
通讯作者：
de Haan, G
影响因子：
30.8
作者：
Chesler, EJ;Lu, L;Williams, RW
通讯作者：
Williams, RW