Abstract
BackgroundMammalian development in utero is absolutely dependent on proper placental development, which is ultimately regulated by the placental genome. The regulation of the placental genome can be directly studied by exploring the underlying organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships.ResultsIn this study, we performed a comprehensive analysis of human placental co-expression using RNA sequencing and intergrated multiple transcriptome datasets spanning human gestation. We identified modules of co-expressed genes that are preserved across human gestation, and also identifed modules conserved in the mouse indicating conserved molecular networks involved in placental development and gene expression patterns more specific to late gestation. Analysis of co-expressed gene flanking sequences indicated that conserved co-expression modules in the placenta are regulated by a core set of transcription factors, including ZNF423 and EBF1. Additionally, we identified a gene co-expression module enriched for genes implicated in the pregnancy pathology preeclampsia. By using an independnet transcriptome dataset, we show that these co-expressed genes are differentially expressed in preeclampsia.ConclusionsThis study represents a comprehensive characterisation of placental co-expression and provides insight into potential transcriptional regulators that govern conserved molecular programs fundamental to placental development.
Highlights
Mammalian development in utero is absolutely dependent on proper placental development, which is regulated by the placental genome
This demonstrated the robust nature of the eigengene for testing for differences in gene regulation between control and PE pregnancies. These results implicate M12 co-expressed genes in PE and suggest that the mechanisms regulating M12 co-expression may be altered in PE. By conducting this comprehensive co-expression network analysis of the human placental transcriptome, we reveal previously unappreciated aspects of transcriptional organisation at the fetal-maternal interface
This analysis entailed the integration of multiple gene expression datasets and curated databases, which enabled the testing of specific hypotheses regarding placental genome regulation
Summary
Mammalian development in utero is absolutely dependent on proper placental development, which is regulated by the placental genome. The regulation of the placental genome can be directly studied by exploring the underlying organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. Placental trophoblast cells begin to invade into the lining of the uterus, where they colonise and transform the mother’s spiral arteries and the extra-embryonic tissue placental tissue establishes its own network of blood vessels Together these processes facilitate the exchange of all nutrients, gases and waste throughout pregnancy. Co-expression analyses that consider the gene-wise relationships in gene expression data have cast new light on previously unappreciated patterns of transcriptional organisation with regards to processes and functions such as lipid metabolism [13], cancer [14], human brain development and neuropathology [15,16,17], and embryonic development [18]. To gain a new perspective on placental genome regulation across human gestation and between human and mouse, we performed a comprehensive analysis of placental gene co-expression
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