Location: Arkansas Children's Nutrition CenterTitle: Placental transcriptome co-expression analysis reveals conserved regulatory program across gestation
|BUCKBERRY, S - University Of Adelaide|
|BIANCO-MIOTTO, T - University Of Adelaide|
|BENT, S - University Of Adelaide|
|CLIFTON, V - University Of Adelaide|
|SHOUBRIDGE, C - University Of Adelaide|
|SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)|
|ROBERTS, C - University Of Adelaide|
Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/7/2016
Publication Date: 1/3/2017
Citation: Buckberry, S., Bianco-Miotto, T., Bent, S.J., Clifton, V., Shoubridge, C., Shankar, K., Roberts, C.T. 2017. Placental transcriptome co-expression analysis reveals conserved regulatory program across gestation. BMC Genomics. 18(1):10. doi:10.1186/s12864-016-3384-9.
Interpretive Summary: Appropriate development of the placenta is essential for a healthy pregnancy, as the placenta provides the primary interface through which all nutrients and gases pass from mother to child. The development of this complex organ is orchestrated through the actions of a number of cell types that occur throughout pregnancy. At a genomic level much less is understood about the molecular players involved in placentation. In this study, we identified genes that track placental development. Analysis of genes whose expression patterns through time shared strong similarities allowed for the discovery of unique regulators of DNA expression, including transcription factors such as ZNF423 and EBF1. These studies provide an important, first-ever resource to study the molecular mechanisms underlying placental development, which is critical to understand the underpinnings of healthy pregnancy and child development.
Technical Abstract: Mammalian 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 organization of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. In this study, we performed a comprehensive analysis of human placental co-expression using RNA sequencing and integrated multiple transcriptome datasets spanning human gestation. We identified modules of co-expressed genes that are preserved across human gestation, and also identified 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 independent transcriptome dataset, we show that these co-expressed genes are differentially expressed in preeclampsia. This study represents a comprehensive characterization of placental co-expression and provides insight into potential transcriptional regulators that govern conserved molecular programs fundamental to placental development.