Myometrial transcriptional signatures of human parturition
File(s)
Author(s)
Type
Journal Article
Abstract
The process of parturition involves the transformation of the quiescent myometrium (uterine smooth muscle) to the highly contractile laboring state. This is thought to be driven by changes in gene expression in myometrial cells. Despite the existence of multiple myometrial gene expression studies, the transcriptional programs that initiate labor are not known. Here, we integrated three transcriptome datasets, one novel (NCBI Gene Expression Ominibus: GSE80172) and two existing, to characterize the gene expression changes in myometrium associated with the onset of labor at term. Computational analyses including classification, singular value decomposition, pathway enrichment, and network inference were applied to individual and combined datasets. Outcomes across studies were integrated with multiple protein and pathway databases to build a myometrial parturition signaling network. A high-confidence (significant across all studies) set of 126 labor genes were identified and machine learning models exhibited high reproducibility between studies. Labor signatures included both known (interleukins, cytokines) and unknown (apoptosis, MYC, cell proliferation/differentiation) pathways while cyclic AMP signaling and muscle relaxation were associated with non-labor. These signatures accurately classified and characterized the stages of labor. The data-derived parturition signaling networks provide new genes/signaling interactions to understand phenotype-specific processes and aid in future studies of parturition.
Date Issued
2019-04-01
Date Acceptance
2019-02-19
Citation
Frontiers in Genetics, 2019, 10
ISSN
1664-8021
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Genetics
Volume
10
Copyright Statement
© 2019 Stanfield, Lai, Lei, Johnson, Blanks, Romero, Chance, Mesiano and Koyutürk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000463108600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
parturition
myometrium
gene expression networks
classification
inflammation
SINGULAR-VALUE DECOMPOSITION
SPONTANEOUS HUMAN LABOR
GENE-EXPRESSION
DIFFERENTIAL GENE
PREGNANCY
PRETERM
REGULARIZATION
MICROARRAY
SELECTION
PATHWAYS
Publication Status
Published
Article Number
ARTN 185
Date Publish Online
2019-04-01