The single-cell atlas of the murine intrauterine tissues during preterm labor
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA823999 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18654204_1.fastq.gz | Fastqsanger.gz | |||
| SRR18654204_2.fastq.gz | Fastqsanger.gz | |||
| SRR18654205_1.fastq.gz | Fastqsanger.gz | |||
| SRR18654205_2.fastq.gz | Fastqsanger.gz | |||
| SRR18654206_1.fastq.gz | Fastqsanger.gz |
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Project description:scRNA-seq was utilized to reveal that preterm labor affects the cellularity of the uterus, decidua, and cervix through immune cell infiltration and altered transcriptomic profiles of non-immune cell types.
2023-01-04 | GSE200289 | GEO
Project description:Preterm birth is multifactorial in origin with several distinct clinical phenotypes of differing etiologies, including idiopathic preterm birth. Preterm birth involves the interaction of genetic, societal and environmental factors such as nutrition, lifestyle and stress that may modulate the length of gestation via the epigenome. DNA methylation is a well-studied epigenetic modification whereby promoter methylation commonly represses gene expression and vice versa. Myometrial tissue was obtained at cesarean section at term with or without labor, preterm without labor, idiopathic preterm labor, and twin gestations with labor. Differences in the myometrial epigenomes were identified at gene promoters, CpG islands, CpG island shores and shelves, gene bodies across the genome between the groups of women with preterm labor of different phenotypes vs. normal term labor. Functional clustering analysis indicated the significantly enriched pathways of hypomethylated genes (permissive) were related to acute inflammatory and acute-phase responses. By contrast, genes that are hypermethylated (repressive) revealed enrichment for contractile fibers and cell. This study provides the first high-resolution DNA methylome of human myometrium with evidence for differences in the methylome that may relate to idiopathic preterm birth via regulation of gene expression. The findings extend previous observations that idiopathic preterm labor is associated with subclinical intrauterine infection and inflammatory pathways and point to targets for further molecular characterization of preterm delivery. Comparison of the human myometrial epigenomes in pregnancies with preterm labor of different phenotypes vs. normal term labor
2017-05-04 | E-GEOD-71123 | biostudies-arrayexpress
Project description:Preterm birth is multifactorial in origin with several distinct clinical phenotypes of differing etiologies, including idiopathic preterm birth. Preterm birth involves the interaction of genetic, societal and environmental factors such as nutrition, lifestyle and stress that may modulate the length of gestation via the epigenome. DNA methylation is a well-studied epigenetic modification whereby promoter methylation commonly represses gene expression and vice versa. Myometrial tissue was obtained at cesarean section at term with or without labor, preterm without labor, idiopathic preterm labor, and twin gestations with labor. Differences in the myometrial epigenomes were identified at gene promoters, CpG islands, CpG island shores and shelves, gene bodies across the genome between the groups of women with preterm labor of different phenotypes vs. normal term labor. Functional clustering analysis indicated the significantly enriched pathways of hypomethylated genes (permissive) were related to acute inflammatory and acute-phase responses. By contrast, genes that are hypermethylated (repressive) revealed enrichment for contractile fibers and cell. This study provides the first high-resolution DNA methylome of human myometrium with evidence for differences in the methylome that may relate to idiopathic preterm birth via regulation of gene expression. The findings extend previous observations that idiopathic preterm labor is associated with subclinical intrauterine infection and inflammatory pathways and point to targets for further molecular characterization of preterm delivery.
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Project description:We compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with preterm prelabor rupture of membranes (PPROM) deliveries to further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events. Chorioamnion, separated into amnion and chorion, was collected from gestationally age-matched cases and controls within 15 minutes of birth, and analyzed using RNA sequencing. In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.
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Project description:Distinct processes govern the transition from myometrial quiescence to activation during both term and preterm labor. We sought the specific gene sets responsible for initiating term and preterm labor, along with a core set of effector genes necessary for labor independent of gestational age and the underlying trigger. The Effector Gene Set consisted of 49 genes present in both preterm and term labor but absent from non-labor samples. 122 genes were specific to preterm labor (Preterm Initiator Set) and 229 to term labor (Term Initiator Set). The Term Initiator and the Effector Sets reflected predominantly inflammatory processes. Surprisingly, the Preterm Initiator Gene Set reflected molecular and biological events almost exclusive of inflammation. Preterm and term labor differ dramatically in their unique, initiator gene profiles, suggesting alternative pathways underlie these events. Inflammatory processes are ubiquitous to the Term Initiator and the Effector Gene Sets, supporting the idea term parturition is an inflammatory process. The absence of inflammatory processes in the Preterm Initiator Set suggests inflammation is secondary to processes triggering spontaneous preterm birth, and could explain the lack of therapeutic efficacy associated with anti inflammatory/antibiotic regimens. Keywords: myometrial gene expression, preterm versus term labor
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Project description:Distinct processes govern the transition from myometrial quiescence to activation during both term and preterm labor. We sought the specific gene sets responsible for initiating term and preterm labor, along with a core set of effector genes necessary for labor independent of gestational age and the underlying trigger. The Effector Gene Set consisted of 49 genes present in both preterm and term labor but absent from non-labor samples. 122 genes were specific to preterm labor (Preterm Initiator Set) and 229 to term labor (Term Initiator Set). The Term Initiator and the Effector Sets reflected predominantly inflammatory processes. Surprisingly, the Preterm Initiator Gene Set reflected molecular and biological events almost exclusive of inflammation. Preterm and term labor differ dramatically in their unique, initiator gene profiles, suggesting alternative pathways underlie these events. Inflammatory processes are ubiquitous to the Term Initiator and the Effector Gene Sets, supporting the idea term parturition is an inflammatory process. The absence of inflammatory processes in the Preterm Initiator Set suggests inflammation is secondary to processes triggering spontaneous preterm birth, and could explain the lack of therapeutic efficacy associated with anti inflammatory/antibiotic regimens. Experiment Overall Design: Myometrial gene expression was analyzed from samples obtained at term (n=6) or preterm (n=6) with and without labor using cDNA microarrays. Patients in preterm labor all had intra amniotic inflammation. Gene sets were generated using logical operations within a functional mapping tool (MetaCoreâ¢, GeneGo, St. Joseph, MI). Relevant gene sets were validated with quantitative real-time polymerase chain reaction.
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Project description:Preterm birth, defined as delivery before the 37th week of gestation, is the most common cause of neonatal mortality and the second leading cause of death in children under five years of age. Preterm birth is associated with immediate and long term morbidity as well as growth and developmental delay. Currently there is no treatment that can prevent or block preterm labor. In order to identify the molecular regulators of preterm spontaneous labor in the human myometrium, we studied the gene expression profiles of samples with Preterm Spontaneous Labour (PSL) and compared them with the gene expression profiles of samples with Preterm No Labor (PNL).
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Project description:Comparing miRNAs expression levels in chorioamniotic membranes from women at term in labor (TL), women at term not in labor (TNL) and women who deliverd preterm (PTLC). The goal was to see if miRNA levels are indicators of preterm delivery or spontaneous labor at term. A two-channel technology was used in this experiment in which a pooled reference RNA was used for competitive hybridization. The pooled reference was generated at Exiqon in Denmark from a mixture of several human tissues (placenta, thyroid, brain, adipose, spleen, liver, colon, skeletal muscle, ovary, kidney, heart, cervix, testes, esophagus, small intestine, prostate, trachea, thymus, bladder, lung).
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Project description:Preterm birth, the leading cause of perinatal morbidity and mortality worldwide, frequently results from the syndrome of preterm labor. The best-established causal link to preterm labor is intra-amniotic infection, which involves premature activation of the parturition cascade in the reproductive tissues. Herein, we utilize single-cell RNA sequencing (scRNA-seq) to generate a single-cell atlas of the murine uterus, decidua, and cervix in a model of infection-induced preterm labor. We show that preterm labor affects the transcriptomic profiles of specific immune and non-immune cell subsets. Shared and tissue-specific gene expression signatures are identified among affected cells. Determination of intercellular communications implicates specific cell types in preterm labor-associated signaling pathways across tissues. In silico comparison of murine and human uterine cell-cell interactions reveals conserved signaling pathways implicated in labor. Thus, our scRNA-seq data provide insights into the preterm labor-driven cellular landscape and communications in reproductive tissues.
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