Integrative transcriptome meta-analysis reveals widespread sex-biased gene expression at the human fetal-maternal interface.

Integrative transcriptome meta-analysis reveals widespread sex-biased gene expression at the human fetal-maternal interface.
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综合转录组荟萃分析揭示了人类胎儿界面的广泛性偏见基因表达。

DOI:
10.1093/molehr/gau035
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发表时间:
2014-08
影响因子:
4
通讯作者:
Roberts CT
Roberts CT
中科院分区:
医学2区
文献类型:
--
作者:
Buckberry S;Bianco-Miotto T;Bent SJ;Dekker GA;Roberts CT

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由于男性和女性共享高度相似的基因组,许多性二态性状的调节被限制通过性别偏向的基因调节发生。有强有力的证据表明,人类男性和女性在子宫内的生长和发育方面存在差异,这些不同的生长策略似乎使男性在次优条件下的风险增加。由于胎盘是整个妊娠期间母胎交换的界面,这些发育差异很可能是由胎盘功能差异引起的。迄今为止,在这一领域的进展一直受到阻碍,缺乏全基因组信息的性别差异胎盘基因表达。因此,我们这项研究的动机是表征人类胎盘中性别偏见的基因表达。我们从11个微阵列数据集中获得了>300个非病理性胎盘样本的基因表达数据,并应用了基于图谱的阵列探针重新注释和逆方差荟萃分析方法,结果显示>140个基因(错误发现率(FDR)<0.05)在男性和女性胎盘之间差异表达。这些基因中的大多数(>60%)是常染色体的,其中许多涉及高水平的调控过程,如基因转录,细胞生长和增殖以及激素功能。特别令人感兴趣的是,我们从LHB-CGB簇中的所有七个基因中检测到更高的女性表达,其中包括参与胎盘发育、妊娠维持和母体免疫耐受的基因。这些结果表明,正常人胎盘中的性别偏向基因表达发生在整个基因组中,包括对生长,发育和维持妊娠至关重要的基因。
As males and females share highly similar genomes, the regulation of many sexually dimorphic traits is constrained to occur through sex-biased gene regulation. There is strong evidence that human males and females differ in terms of growth and development in utero and that these divergent growth strategies appear to place males at increased risk when in sub-optimal conditions. Since the placenta is the interface of maternal–fetal exchange throughout pregnancy, these developmental differences are most likely orchestrated by differential placental function. To date, progress in this field has been hampered by a lack of genome-wide information on sex differences in placental gene expression. Therefore, our motivation in this study was to characterize sex-biased gene expression in the human placenta. We obtained gene expression data for >300 non-pathological placenta samples from 11 microarray datasets and applied mapping-based array probe re-annotation and inverse-variance meta-analysis methods which showed that >140 genes (false discovery rate (FDR) <0.05) are differentially expressed between male and female placentae. A majority of these genes (>60%) are autosomal, many of which are involved in high-level regulatory processes such as gene transcription, cell growth and proliferation and hormonal function. Of particular interest, we detected higher female expression from all seven genes in the LHB-CGB cluster, which includes genes involved in placental development, the maintenance of pregnancy and maternal immune tolerance of the conceptus. These results demonstrate that sex-biased gene expression in the normal human placenta occurs across the genome and includes genes that are central to growth, development and the maintenance of pregnancy.
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