Epigenetic alterations affecting transcription factors and signaling pathways in stromal cells of endometriosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA347648 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4413220_1.fastq.gz | Fastqsanger.gz | |||
| SRR4413220_2.fastq.gz | Fastqsanger.gz | |||
| SRR4413230_1.fastq.gz | Fastqsanger.gz | |||
| SRR4413230_2.fastq.gz | Fastqsanger.gz | |||
| SRR4413240_1.fastq.gz | Fastqsanger.gz |
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Project description:Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains. Genes found to have DM included examples encoding transporters (SLC22A23), signaling components (BDNF, DAPK1, ROR1, and WNT5A) and transcription factors (GATA family, HAND2, HOXA cluster, NR5A1, OSR2, TBX3). Intriguingly, among the TF genes with DM we also found JAZF1, a proto-oncogene affected by chromosomal translocations in endometrial stromal tumors. Using RNA-Seq we identified a subset of the DM genes showing differential expression (DE), with the likelihood of DE increasing with the extent of the DM and its location in enhancer elements. Supporting functional relevance, treatment of stromal cells with the hypomethylating drug 5aza-dC led to activation of DAPK1 and SLC22A23 and repression of HAND2, JAZF1, OSR2, and ROR1 mRNA expression. We found that global 5hmC is decreased in endometriotic versus normal stroma, and for JAZF1 and BDNF examined by oxidative bis-seq, found that when 5hmC is detected, patterns of 5hmC paralleled those of 5mC. Together with prior studies, these results define a consistent epigenetic signature in endometriosis stromal cells and nominate specific transcriptional and signaling pathways as therapeutic targets.
2017-01-13 | GSE87809 | GEO
Project description:Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains. Genes found to have DM included examples encoding transporters (SLC22A23), signaling components (BDNF, DAPK1, ROR1, and WNT5A) and transcription factors (GATA family, HAND2, HOXA cluster, NR5A1, OSR2, TBX3). Intriguingly, among the TF genes with DM we also found JAZF1, a proto-oncogene affected by chromosomal translocations in endometrial stromal tumors. Using RNA-Seq we identified a subset of the DM genes showing differential expression (DE), with the likelihood of DE increasing with the extent of the DM and its location in enhancer elements. Supporting functional relevance, treatment of stromal cells with the hypomethylating drug 5aza-dC led to activation of DAPK1 and SLC22A23 and repression of HAND2, JAZF1, OSR2, and ROR1 mRNA expression. We found that global 5hmC is decreased in endometriotic versus normal stroma, and for JAZF1 and BDNF examined by oxidative bis-seq, found that when 5hmC is detected, patterns of 5hmC paralleled those of 5mC. Together with prior studies, these results define a consistent epigenetic signature in endometriosis stromal cells and nominate specific transcriptional and signaling pathways as therapeutic targets.
2017-01-13 | GSE87621 | GEO
Project description:Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains. Genes found to have DM included examples encoding transporters (SLC22A23), signaling components (BDNF, DAPK1, ROR1, and WNT5A) and transcription factors (GATA family, HAND2, HOXA cluster, NR5A1, OSR2, TBX3). Intriguingly, among the TF genes with DM we also found JAZF1, a proto-oncogene affected by chromosomal translocations in endometrial stromal tumors. Using RNA-Seq we identified a subset of the DM genes showing differential expression (DE), with the likelihood of DE increasing with the extent of the DM and its location in enhancer elements. Supporting functional relevance, treatment of stromal cells with the hypomethylating drug 5aza-dC led to activation of DAPK1 and SLC22A23 and repression of HAND2, JAZF1, OSR2, and ROR1 mRNA expression. We found that global 5hmC is decreased in endometriotic versus normal epithelial but not stroma cells, and for JAZF1 and BDNF examined by oxidative bis-seq, found that when 5hmC is detected, patterns of 5hmC paralleled those of 5mC. Together with prior studies, these results define a consistent epigenetic signature in endometriosis stromal cells and nominate specific transcriptional and signaling pathways as therapeutic targets.
| S-EPMC5268815 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-01-13 | GSE87810 | GEO
Project description:Gene expression profiling of primary stromal cell cultures isolated from human endometrium and ovarian endometriosis. Samples are derived from the endometrium of 6 healthy patients and the endometriomas of 6 diseased patients. The results indicate the gene expression differences between these two cell populations. Stromal cells were obtained from human normal endometrial tissues and ovarian endometriomas. The tissues were digested enzymatically, and pure stromal cell populations were established.
2014-08-01 | E-GEOD-58178 | biostudies-arrayexpress
Project description:Gene expression profiling of primary stromal cell cultures isolated from human endometrium and ovarian endometriosis. Samples are derived from the endometrium of 6 healthy patients and the endometriomas of 6 diseased patients. The results indicate the gene expression differences between these two cell populations.
2014-08-01 | GSE58178 | GEO
Project description:Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P4) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P4, we compared early (6-h), intermediate (48-h), and late (14-day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESFs) from women with endometriosis (hESFendo) to hESFs from women without endometriosis (hESFnonendo). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESFs were isolated and treated with P4 (1 μM) plus estradiol (E2) (10 nM), E2 alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P4 in both hESFnonendo and hESFendo, although a blunted response to P4 was observed in the latter. The normal response of hESF to P4 involves a tightly regulated kinetic cascade involving key components in the P4 receptor and MAPK signaling pathways that results in inhibition of E2-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESFendo early response to P4. The abnormal response of this cell type to P4 may contribute to compromised embryonic implantation and infertility in women with endometriosis. We compared early (6-h), intermediate (48-h), and late (14-day) in vitro whole-genome responses of hESF from women with endometriosis (hESFendo) to hESF from women without endometriosis (hESFnonendo) treated with P4 plus E2 (E2P4), E2 alone, or vehicle alone. Using this experimental paradigm, the data demonstrate unique phenotypes, gene expression processes, biochemical and signaling pathways, and networks suggestive of early, intermediate, and late responses of hESFnonendo and hESFendo to P4, giving insights into the complexity of events occurring normally in response to P4 and in the setting of endometriosis.
2012-01-24 | E-GEOD-35287 | biostudies-arrayexpress
Project description:It is hypothesized that impaired endometrial decidualization contributes to decreased fertility in endometriosis patients. To identify the molecular defects that underpin defective decidualization in endometriosis, we subjected endometrial stromal cells from healthy individuals or with endometriosis to time course in vitro decidualization with estradiol, progesterone, and 8-bromo-cyclic-AMP (EPC) for 2, 4, 6, or 8 days. Transcriptomic profiling identified novel differences in key pathways between normal and endometriosis, including defective bone morphogenetic protein (BMP) signaling (ID1, ID2, ID3, BMP6), altered iron transport (SLC40A1, TFRC), endometrial stem cell markers (CD44, SUSD2), and retinoid signaling pathways (RORB, ALDH1L1, RARA). Genome-wide binding analyses identified an altered genomic distribution of SMAD4 in decidualized stromal cells from endometriosis patients relative to normal individuals, with an overrepresentation of gene ontologies related to signaling by transforming growth factor β (TGFβ), neurotrophic tyrosine kinase receptors (NTRK), and nerve growth factor (NGF)-stimulated transcription. We found that direct SMAD1/5/4 target genes control FOXO, PI3K/AKT, and progesterone-mediated signaling in decidualizing cells and that BMP2 supplementation of patient-derived assembloids from endometriosis patients restored decidualization. In summary, transcriptomic and genomic profiling of patient-derived endometrial cells and assembloids identified that restoring BMP/SMAD1/5/4 signaling is crucial for engaging a robust decidualization program in women with endometriosis.
2024-02-17 | GSE243156 | GEO
Project description:It is hypothesized that impaired endometrial decidualization contributes to decreased fertility in endometriosis patients. To identify the molecular defects that underpin defective decidualization in endometriosis, we subjected endometrial stromal cells from healthy individuals or with endometriosis to time course in vitro decidualization with estradiol, progesterone, and 8-bromo-cyclic-AMP (EPC) for 2, 4, 6, or 8 days. Transcriptomic profiling identified novel differences in key pathways between normal and endometriosis, including defective bone morphogenetic protein (BMP) signaling (ID1, ID2, ID3, BMP6), altered iron transport (SLC40A1, TFRC), endometrial stem cell markers (CD44, SUSD2), and retinoid signaling pathways (RORB, ALDH1L1, RARA). Genome-wide binding analyses identified an altered genomic distribution of SMAD4 in decidualized stromal cells from endometriosis patients relative to normal individuals, with an overrepresentation of gene ontologies related to signaling by transforming growth factor β (TGFβ), neurotrophic tyrosine kinase receptors (NTRK), and nerve growth factor (NGF)-stimulated transcription. We found that direct SMAD1/5/4 target genes control FOXO, PI3K/AKT, and progesterone-mediated signaling in decidualizing cells and that BMP2 supplementation of patient-derived assembloids from endometriosis patients restored decidualization. In summary, transcriptomic and genomic profiling of patient-derived endometrial cells and assembloids identified that restoring BMP/SMAD1/5/4 signaling is crucial for engaging a robust decidualization program in women with endometriosis.
2024-02-17 | GSE243039 | GEO
Project description:It is hypothesized that impaired endometrial decidualization contributes to decreased fertility in endometriosis patients. To identify the molecular defects that underpin defective decidualization in endometriosis, we subjected endometrial stromal cells from healthy individuals or with endometriosis to time course in vitro decidualization with estradiol, progesterone, and 8-bromo-cyclic-AMP (EPC) for 2, 4, 6, or 8 days. Transcriptomic profiling identified novel differences in key pathways between normal and endometriosis, including defective bone morphogenetic protein (BMP) signaling (ID1, ID2, ID3, BMP6), altered iron transport (SLC40A1, TFRC), endometrial stem cell markers (CD44, SUSD2), and retinoid signaling pathways (RORB, ALDH1L1, RARA). Genome-wide binding analyses identified an altered genomic distribution of SMAD4 in decidualized stromal cells from endometriosis patients relative to normal individuals, with an overrepresentation of gene ontologies related to signaling by transforming growth factor β (TGFβ), neurotrophic tyrosine kinase receptors (NTRK), and nerve growth factor (NGF)-stimulated transcription. We found that direct SMAD1/5/4 target genes control FOXO, PI3K/AKT, and progesterone-mediated signaling in decidualizing cells and that BMP2 supplementation of patient-derived assembloids from endometriosis patients restored decidualization. In summary, transcriptomic and genomic profiling of patient-derived endometrial cells and assembloids identified that restoring BMP/SMAD1/5/4 signaling is crucial for engaging a robust decidualization program in women with endometriosis.
2024-02-17 | GSE243157 | GEO