Location: Arkansas Children's Nutrition CenterTitle: Transcriptomic and epigenomic landscapes during cell fusion in BeWo trophoblast cells
|SHANKAR, K - Arkansas Children'S Nutrition Research Center (ACNC)|
|KANG, P - Arkansas Children'S Nutrition Research Center (ACNC)|
|ZHONG, Y - Arkansas Children'S Nutrition Research Center (ACNC)|
|BORENGASSER, S - University Of Colorado|
|WINGFIELD, C - University Arkansas For Medical Sciences (UAMS)|
|SABEN, J - Washington University School Of Medicine|
|GOMEZ-ACEVEDO, H - Arkansas Children'S Nutrition Research Center (ACNC)|
|THAKALI, K - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: Placenta
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/13/2015
Publication Date: 12/1/2015
Citation: Shankar, K., Kang, P., Zhong, Y., Borengasser, S.J., Wingfield, C., Saben, J., Gomez-Acevedo, H., Thakali, K.M. 2015. Transcriptomic and epigenomic landscapes during cell fusion in BeWo trophoblast cells. Placenta. 36(12):1342-1351.
Interpretive Summary: The placenta is the earliest organ of the baby to develop in the womb and is entrusted with the transport of nutrients and gases to support development. Specific cells in the placenta also represent the actual barrier between mother and baby through which all signals and nutrients are exchanged, and development of this barrier is mission-critical to a successful pregnancy. Using a variety of molecular approaches we examined the process by which this barrier is formed and continually sustained using a model cell system followed by confirmatory studies in human placenta at term. The studies revealed the involvement of a unique epigenetic process (a way of controlling what's expressed from the genetic code, DNA) in the formation of this barrier. These studies are important as the placenta is now recognized to play an important role in dictating life-long health of the child. Hence, maternal nutritional and health status may affect child health via changes in fundamentally altering placental development.
Technical Abstract: Syncytialization is a process essential to the genesis and vitality of the decisive maternal-fetal interface, the syncytiotrophoblast. While the role of specific genes important in syncytial fusion is appreciated, an integrated global analysis of syncytialization is absent. We leveraged a variety of approaches (RNA-seq, genome-scale DNA methylation and ChIP-seq) to assemble a genome-wide transcriptomic and epigenomic view of syncytialization in BeWo cells. RNA-seq analysis of expression profiles revealed alterations in ~3000 genes over the 3 day time-course of forskolin, including identification of several previously unrecognized genes to be involved in syncytialization. These genes were enriched for cell differentiation, morphogenesis, blood vessel and placental labyrinth development and steroid hormone response. Genome-scale DNA methylation via reduced representation bisulfite sequencing (RRBS) showed altered methylation of a number of CpGs associated with cell differentiation and commitment. Finally, genome-wide localization of seven key histone marks encompassing permissive (H3K4me3, H3K9ac, H3K27ac), enhancer (H3K4me1), elongation (H3K36me3) and repressive (H3K27me3, H3K9me3) states was performed via ChiP-seq. These analyses clearly revealed that syncytialization was associated with a gain in transcriptionally permissive/active marks (H3K4me3, K9ac, K27ac and K36me3) among genes that are either constitutive or upregulated in syncytialization. Overall, these results provide a novel resource to elucidate the underlying epigenetic mechanisms coordinating transcriptional changes associated with syncytialization in BeWo cells.