Nonpregnant and term pregnant human myometrial tissues
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ABSTRACT:
PROVIDER: PRJNA565907 | ENA |
REPOSITORIES: ENA
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Project description:The myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were subject to RNAseq, ATAC-seq and PGR ChIP-seq assays to profile transcriptome, assessible genome and PGR occupancy.
2019-11-28 | GSE137551 | GEO
Project description:Transcriptomic profiles of nonpregnant and term pregnant human myometrial tissues
| PRJNA565908 | ENA
Project description:The open chromatin regions of nonpregnant and term pregnant human myometrial tissues were assessed by ATAC-seq to gain insight on potential genome regulatory elements in vivo. patterns of accessible genome change between NP and TP myometrium, leading to altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors and MEF2A transcription factors.
2019-11-28 | GSE137549 | GEO
Project description:Profiles of PGR genome occupancy in human myometrial specimens were documented by ChIP-seq to investigate downstream targets of the progesterone receptor and candidate partner transcription regulators at the nonpregnant and term pregnant stages.
2019-11-28 | GSE137550 | GEO
Project description:The goal of this study was to select the optimal myometrial cells for our high-throughput drug discovery assay, as well as determine the similarity or differences of myometrial cells to vascular smooth muscle cells (VSMCs)-the most common off-target of current myometrial therapeutics. RNA-seq was used to: 1) identify which myometrial cells retained the most similar transcriptome profile to native tissue, and 2) compare the uterine myometrial transcriptome to VSMCs in hopes of identifying a uterine-selective transcriptome that was “druggable” for tocolytic or uterotonic use. Four sources of myometrial cells were examined: 1) term pregnant human primary myometrial cells isolated from tissue biopsies obtained at the time of caesarean sections, 2) term pregnant mouse primary myometrial cells, 3) commercially-available immortalized pregnant human myometrial (PHM1) cells and 4) human telomerase immortalized myometrial (hTERT-HM) cells. Correlation analysis of aligned reads identified that the transcriptome of primary human myometrial and hTERT-HM cells showed 85% and 80% correlation, respectively, to human myometrial tissue and that the transcriptome of hTERT-HM and PHM1 cells is 90% or more correlative to human primary myometrial cells. The expression levels (fold-change) of contraction-associciated transcripts (OXTR, PTGFR, PTGS2 and GJA1) strongly correlated (r=0.93) between RNA sequencing and qRT-PCR analysis. Analysis of aligned reads among myometrial cells revealed the number of differentially expressed transcripts (fold-change≥2.0, adjusted p-value≤0.01) relative to primary human myometrial cells: hTERT-HM (946 upregulated and 2,351 downregulated), PHM1 (1,575 upregulated and 2,415 downregulated) and primary mouse myometrial cells (3,435 upregulated and 2,966 downregulated). Correlation analysis showed that the human primary myometrial cell transcriptome is over 90% similar to the transcriptome of VSMCs examined. A number of genes associated with smooth muscle contractile machinery (TPM1, TPM2, CNN1, CALD1, ACTA2 and PLN)were significantly (p≤0.01) upregulated (≥2-fold) in human primary myometrial compared to vascular SMCs. We identified 498 transcripts were identified as upregulated in human primary myometrial cells compared to all three VSMCs examined. Of these, the drug-gene interaction database identified 142 genes as druggable
2020-04-14 | GSE125701 | GEO
Project description:Profiling open chromatin regions in human myometrial tissues
| PRJNA565904 | ENA
Project description:Purpose: To chart the human myometrial transcriptomes before and after the onset of labour. Methods: Tophat splice junction mapping of paired-end reads, HTSeq to generate counts, cufflinks to track transcripts, DESeq, edgeR and baySeq to detect differentially expressed genes and principal component analysis for clustering analyses. Results: We mapped on average 14 million paired-end reads per sample (counting each end individually) to the human genome (build hg19) and covered the expressed transcriptome about 13 times with a TopHat-HTSeq workflow. We performed a comparative analysis with an analogous microarray study (Mittal et al., 2010) and found some overlap between the RNA-seq and the microarray data. Conclusions: Our study is the first RNA-seq study of the human myometrium before and after the onset of labour. We show that while microarray and RNA-seq studies may complement each other, RNA-seq has a much greater resolution. At term with and at term without labour human myometrial mRNA profiles were generated by deep sequencing, using Illumina GAIIx (five biological replicates each).
2014-02-17 | E-GEOD-50599 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-11-27 | GSE137552 | GEO
Project description:The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were used for genome-wide analyses to elucidate potential future preventive or therapeutic targets involved in the regulation of labor. Using myometrial tissues directly subjected to RNA sequencing (RNA-seq), progesterone receptor (PGR) chromatin immunoprecipitation sequencing (ChIP-seq), and histone modification ChIP-seq, we profiled genome-wide changes associated with gene expression in myometrial smooth muscle tissue in vivo. In TIL myometrium, PGR occupied predominatly promoter regions including the classical progesterone response element, whereas it bound predominantly to intergenic regions in TNIL myometrial tissue. Differential binding analysis uncovered over 1700 differential PGR-bound sites between TIL and TNIL with 1361 sites gained and 428 lost in labor. Functional analysis identified multiple pathways involved in cAMP-mediated signaling enriched in labor. A three-way integration of the data for ChIP-seq, RNA-seq and active histone marks uncovered the following genes associated with PGR binding, transcriptional activation and altered mRNA levels: ATP11A, CBX7, and TNS1. In vitro studies showed that ATP11A, CBX7, and TNS1 are progesterone responsive. We speculate that these genes may contribute to the contractile phenotype of the myometrium during various stages of labor. In conclusion, we provide novel labor associated genome-wide events and PGR-target genes that can serve as targets for future mechanistic studies.
2022-05-05 | GSE202028 | GEO
Project description:The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were used for genome-wide analyses to elucidate potential future preventive or therapeutic targets involved in the regulation of labor. Using myometrial tissues directly subjected to RNA sequencing (RNA-seq), progesterone receptor (PGR) chromatin immunoprecipitation sequencing (ChIP-seq), and histone modification ChIP-seq, we profiled genome-wide changes associated with gene expression in myometrial smooth muscle tissue in vivo. In TIL myometrium, PGR occupied predominatly promoter regions including the classical progesterone response element, whereas it bound predominantly to intergenic regions in TNIL myometrial tissue. Differential binding analysis uncovered over 1700 differential PGR-bound sites between TIL and TNIL with 1361 sites gained and 428 lost in labor. Functional analysis identified multiple pathways involved in cAMP-mediated signaling enriched in labor. A three-way integration of the data for ChIP-seq, RNA-seq and active histone marks uncovered the following genes associated with PGR binding, transcriptional activation and altered mRNA levels: ATP11A, CBX7, and TNS1. In vitro studies showed that ATP11A, CBX7, and TNS1 are progesterone responsive. We speculate that these genes may contribute to the contractile phenotype of the myometrium during various stages of labor. In conclusion, we provide novel labor associated genome-wide events and PGR-target genes that can serve as targets for future mechanistic studies.
2022-05-05 | GSE202027 | GEO