Expression profiles of four hematopoietic cell types isolated from the bone marrow of BXD recombinant inbred mice.. Mus musculus

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 (1283) 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. Overall design: These data consist of total mRNA obtained from purified Lin-Sca-1+c-Kit+ multi-lineage cells, committed Lin-Sca-1-c-Kit+ progenitor cells, erythroid TER-119+ cells, and myeloid Gr-1+ cells, isolated from the bone marrow of ~25 genetically related and fully genotyped BXD – C57BL/6 (B6) X DBA/2 (D2) – recombinant inbred mouse strains (female) in three batches. Samples were assayed in three batches which are labeled in the metadata provided here. Some BXD lines have biological replicates, they are designated with letters (e.g. BXD28a and BXD28b are biological replicates). For some mice, not all four cell populations could be assayed. There are also a few technical replicates (see description column).

遗传基因组学（Genetical genomics）是一种将基因表达变异定位至表达数量性状位点（expression quantitative trait loci, eQTLs）的研究策略。本研究在源自BXD重组近交系小鼠群体的四类功能迥异但发育关联紧密的造血细胞群中开展了遗传基因组学实验。本分析得以探究不同细胞分化状态下eQTL的稳定性与敏感性。尽管我们鉴定出365个"静态"eQTL，在全部四类细胞中均持续活跃；但发现了数量更多的1283个"动态"eQTL，表现出细胞类型依赖性。其中，分别有140、45、531、295个动态eQTL优先在干细胞、祖细胞、红细胞系细胞和髓系细胞中激活。对这些动态eQTL的详细研究显示，在多数情况下eQTL的特异性与靶基因的表达变化存在关联。本研究未发现存在由不同细胞类型中不同eQTL调控的靶基因的证据，这表明功能调控网络内的大规模改变并不常见。本研究结果证实，基因表达的遗传差异对所研究细胞群的发育阶段具有高度敏感性。因此，未来的遗传基因组学研究应聚焦于多种定义明确且高度纯化的细胞类型，以尽可能全面地刻画动态变化的功能调控关系。
整体实验设计：本数据集包含从四类细胞中提取的总mRNA：纯化的Lin-Sca-1+c-Kit+多谱系细胞、定型Lin-Sca-1-c-Kit+祖细胞、红细胞系TER-119+细胞以及髓系Gr-1+细胞，这些细胞均分离自约25个遗传相关且已完成全基因分型的BXD-C57BL/6 (B6) × DBA/2 (D2)重组近交系雌性小鼠的骨髓，样本分三批完成实验。样本的批次信息已在本文提供的元数据中标注。部分BXD品系设有生物学重复，以字母后缀区分（例如BXD28a与BXD28b即为生物学重复样本）。部分小鼠无法完成全部四类细胞群的检测。此外还存在少量技术重复样本（详见元数据的描述列）。