Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide transcriptome alternation by DNA methylation inhibitor 5'-Aza in primary leiomyoma cells

ABSTRACT: Uterine leiomyomas (LM) affect up to 80% of all reproductive-age women. LM growth requires progesterone, progesterone receptor (PGR), and the maintenance and proliferation of a small (5%) stem cell population. Stem cell activation and differentiation are driven by DNA methylation and nuclear hormone receptor action, but crosstalk between these mechanisms remains unclear. We performed an integrated analysis of the transcriptome and epigenetic landscape of LM cells at three differentiation stages and the PGR cistrome of whole LM tissue. The PGR-deficient stem cell population harbored a unique methylation landscape, with hypermethylation at the PGR gene locus and PGR-binding regions, which suppressed stem cell responsiveness to progesterone. The DNA methylation inhibitor 5’-Aza upregulated the expression of PGR and its target genes by stimulating PGR recruitment to the targeted gene loci, and significantly depleted the LM stem cell population and its tumor-initiating capacity. We herein provided mechanistic insights via therapeutically accelerating the stem cell differentiation process of a hormone-sensitive tumor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE138045 | GEO | 2020/10/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide transcriptome profiling of primary human uterine leiomyoma cell populations

Project description:Uterine leiomyomas (LM) affect up to 80% of all reproductive-age women. LM growth requires progesterone, progesterone receptor (PGR), and the maintenance and proliferation of a small (5%) stem cell population. Stem cell activation and differentiation are driven by DNA methylation and nuclear hormone receptor action, but crosstalk between these mechanisms remains unclear. We performed an integrated analysis of the transcriptome and epigenetic landscape of LM cells at three differentiation stages and the PGR cistrome of whole LM tissue. The PGR-deficient stem cell population harbored a unique methylation landscape, with hypermethylation at the PGR gene locus and PGR-binding regions, which suppressed stem cell responsiveness to progesterone. The DNA methylation inhibitor 5’-Aza upregulated the expression of PGR and its target genes by stimulating PGR recruitment to the targeted gene loci, and significantly depleted the LM stem cell population and its tumor-initiating capacity. We herein provided mechanistic insights via therapeutically accelerating the stem cell differentiation process of a hormone-sensitive tumor.

2020-10-01 | GSE138048 | GEO

Genome-wide DNA methylation mapping of primary human uterine leiomyoma cell populations

2020-10-01 | GSE138047 | GEO

Genome-wide H3K4me3 and H3K27Ac profilings of primary human uterine leiomayoma (LM) cell populations

2020-10-01 | GSE138046 | GEO

DNA methylome regulation by progesterone receptor in primary leiomyoma cells

2021-08-01 | GSE148256 | GEO

Genome-wide transcriptome regulation by progesterone receptor in primary leiomyoma cells

2021-08-01 | GSE138050 | GEO

Genome-wide prgesterone receptor binding profile in human uterine leiomyoma tissue

2021-08-01 | GSE138049 | GEO

Genome-wide binding sites of Progesterone receptor (PGR) isoforms PGR-A and PGR-B during differentiation of human endometrial stromal cells

Project description:We report the genome-wide binding sites of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells that express either PGR-A or PGR-B. Progesterone, acting through the progesterone receptors (PGRs), is one of the most critical regulators of endometrial differentiation, known as decidualization, which is a key step toward the establishment of pregnancy. Yet a long-standing unresolved issue in uterine biology is the precise roles played by the major PGR isoforms, PGR-A and PGR-B, during decidualization in the human. Our approach, expressing PGR-A and PGR-B individually after silencing endogenous PGRs in human endometrial stromal cells (HESC), enabled the analysis of the roles of these isoforms separately as well as jointly by ChIP-seq and gene-expression analysis. In order to study the cistromes of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells, we generated primary cultures of human endometrial stromal cells expressing flag tagged PGR-A and PGR-B individually after silencing endogenous PGRs. Input DNA was used as the reference sample.

2015-04-27 | E-GEOD-62475 | biostudies-arrayexpress

RNA-seq of wild-type and PGR (progesterone receptor) knockout pluripotent mouse EpiSCs (epiblast stem cells) and differentiated samples derived from these cell lines (primitive streak and mesoderm)

Project description:EpiSCs (epiblast stem cells) are murine pluripotent stem cells derived from the epiblast of a post-implantation embryo. These cells are primed to differentiate towards embryonic germ layers and are a useful model to study these early developmental events. PGR (progesterone receptor) is a nuclear receptor described mainly in the context of fertility and breast cancer. We noticed that it is also a TF that is expressed in primed EpiSCs, but not in naive mESCs and is further upregulated during mesoderm specification. We hypothesized that it is involved in differentiation to primitive streak and mesoderm progenitors. To test this hypothesis we generated EpiSCs with a genetic knockout of PGR using CRISPR-Cas9-mediated knock-in of an antibiotic resistance cassette. Differentiation of the wild-type and knockout cells and comparison of the different cell types allowed us to conclude that PGR is important for acquiring extraembryonic mesoderm fate and modulates cardiac differentiation, specifically it ensures that correct pools of FHF (first heart field) and SHF (second heart field) are being produced. Our study sheds light on previously unappreciated role of PGR in early embryonic development.

2022-11-30 | E-MTAB-12104 | biostudies-arrayexpress

Genome-wide binding sites of Progesterone receptor (PGR) isoforms PGR-A and PGR-B during differentiation of human endometrial stromal cells

2015-04-27 | GSE62475 | GEO

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities

Project description:The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin–DNA–RNA–protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor–positive and –negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology. PMID: 29921600 (Table S5 and Table S7)

| MSV000079330 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data