Placental transcriptome co-expression analysis reveals conserved regulatory programs across gestation

Sam Buckberry; Tina Bianco-Miotto; Stephen J. Bent; Vicki Clifton; Cheryl Shoubridge; Kartik Shankar; Claire T. Roberts

doi:10.1186/s12864-016-3384-9

Placental transcriptome co-expression analysis reveals conserved regulatory programs across gestation

Sam Buckberry, Tina Bianco-Miotto, Stephen J. Bent, Vicki Clifton, Cheryl Shoubridge, Kartik Shankar, Claire T. Roberts

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Abstract

Background: 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 organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. Results: In 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. Conclusions: This 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.

Original language	English
Article number	10
Pages (from-to)	1-13
Number of pages	13
Journal	BMC Genomics
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s12864-016-3384-9
Publication status	Published - 3 Jan 2017
Externally published	Yes

Bibliographical note

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. © 2020 BioMed Central Ltd.

Keywords

Co-expression
Gene expression
Microarray
Placenta
Preeclampsia
RNA-seq
RNA sequencing

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Buckberry_Placental_P2017Final published version, 2.09 MBLicence: CC BY

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title = "Placental transcriptome co-expression analysis reveals conserved regulatory programs across gestation",

abstract = "Background: 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 organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. Results: In 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. Conclusions: This 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.",

keywords = "Co-expression, Gene expression, Microarray, Placenta, Preeclampsia, RNA-seq, RNA sequencing",

author = "Sam Buckberry and Tina Bianco-Miotto and Bent, {Stephen J.} and Vicki Clifton and Cheryl Shoubridge and Kartik Shankar and Roberts, {Claire T.}",

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AU - Shankar, Kartik

AU - Roberts, Claire T.

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N2 - Background: 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 organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. Results: In 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. Conclusions: This 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.

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Placental transcriptome co-expression analysis reveals conserved regulatory programs across gestation

Abstract

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Keywords

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