The effect of freeze-thaw cycles on gene expression levels in lymphoblastoid cell lines.
The effect of freeze-thaw cycles on gene expression levels in lymphoblastoid cell lines.
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DOI：
10.1371/journal.pone.0107166
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gilad Y
中科院分区：
文献类型：
--
作者：
Çalışkan M;Pritchard JK;Ober C;Gilad Y
eb病毒（EBV）转化淋巴母细胞样细胞系（LCLs）是一种广泛用于人类功能基因组研究的可再生资源。从完整的基因组序列到详细的基因调控谱，积累与相同单个细胞系相关的多维数据的能力进一步增强了lcl作为模型系统的实用性。然而，lcl在多大程度上是一个忠实的模型系统是相对未知的。我们之前已经表明，新建立的lcl的基因表达谱保持了很强的个体成分。在这里，我们扩展了我们的研究，以研究冻融循环对成熟LCLs基因表达模式的影响，特别是在基因表达的个体间差异的背景下。我们报告了新建立的和成熟的lcl的基因表达谱的深刻差异。一旦新建立的lcl经历冻融循环，个体特异性基因表达特征变得不那么明显，因为来自不同个体的lcl中的基因表达水平趋同于更统一的剖面，这反映了成熟转化的B细胞表型。我们发现，先前鉴定的eqtl在相对较少的基因中富集，这些基因在成熟lcl中的调控保持着显著的个体特征。因此，我们得出结论，虽然从成熟LCL的基因调控研究中得出的见解通常不会受到LCL模型系统人工性质的影响，但在成熟LCL培养物中无法观察和研究原代B细胞生物学的许多方面。
Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs) are a widely used renewable resource for functional genomic studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. However, the extent to which LCLs are a faithful model system is relatively unknown. We have previously shown that gene expression profiles of newly established LCLs maintain a strong individual component. Here, we extend our study to investigate the effect of freeze-thaw cycles on gene expression patterns in mature LCLs, especially in the context of inter-individual variation in gene expression. We report a profound difference in the gene expression profiles of newly established and mature LCLs. Once newly established LCLs undergo a freeze-thaw cycle, the individual specific gene expression signatures become much less pronounced as the gene expression levels in LCLs from different individuals converge to a more uniform profile, which reflects a mature transformed B cell phenotype. We found that previously identified eQTLs are enriched among the relatively few genes whose regulations in mature LCLs maintain marked individual signatures. We thus conclude that while insight drawn from gene regulatory studies in mature LCLs may generally not be affected by the artificial nature of the LCL model system, many aspects of primary B cell biology cannot be observed and studied in mature LCL cultures.
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影响因子：
64.8
作者：
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通讯作者：
Skol, Andrew
影响因子：
9.8
作者：
Schadt EE;Molony C;Chudin E;Hao K;Yang X;Lum PY;Kasarskis A;Zhang B;Wang S;Suver C;Zhu J;Millstein J;Sieberts S;Lamb J;GuhaThakurta D;Derry J;Storey JD;Avila-Campillo I;Kruger MJ;Johnson JM;Rohl CA;van Nas A;Mehrabian M;Drake TA;Lusis AJ;Smith RC;Guengerich FP;Strom SC;Schuetz E;Rushmore TH;Ulrich R
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4.5
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通讯作者：
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影响因子：
3.7
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通讯作者：
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