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Deciphering ESR1-driven transcription in human endometrial stromal cells via transcriptome, cistrome, and integration with chromatin landscape [ESR1_RNAseq]

GSE295509 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/05/12 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
12 samples: 3 × NT gRNA Veh vs 3 × NT gRNA E2 vs 3 × ESR1 gRNA Veh vs 3 × ESR1 gRNA E2Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Deciphering estrogen receptor alpha-driven transcription in human endometrial stromal cells via transcriptome, cistrome, and integration with chromatin landscapeF&S science · 2026
Summary (written by the submitters)
Estrogen (E2) acting through the estrogen receptor alpha (ESR1) is a critical regulator of endometrial growth, differentiation and disease. The endometrial stromal cell (ESC) is a key target of ESR1 action and plays a crucial role in regulating paracrine communication to control uterine function. A mechanistic understanding of the role of ESR1 in ESCs is limited by low levels of expression of ESC lines.
Read the full summary ↓
Here we engineered telomerase-immortalized hESC (THESC) to express the CRISPR activation system to activate ESR1. Among six tested guide RNAs, the ESR1-3 gRNA induced robust ESR1 activation, restoring E2 responsiveness in THESC. Bulk RNA-seq revealed ESR1-mediated E2-dependent and E2-independent transcriptional programs, regulating pathways involved in inflammation, proliferation, extracellular matrix organization, and cancer. Notably, 72% of differentially expressed genes (DEGs) overlapped with genes active in human endometrial tissue during the proliferative E2 dominant phase, supporting their physiological relevance. Cut&Run-seq identified genome-wide ESR1 binding sites, with most located at distal regulatory elements. To associate distal ESR1 binding sites with genes, we integrated H3K27ac HiChIP chromatin loops in hESC to identify distal ESR1 binding sites that loop to gene promoters. We identified genes regulated by ESR1/E2 through long-range chromatin looping that are involved in stromal cell decidualization, including FOXO1 and IL6R. Additionally, we identified genes implicated in endometrial cancer, including ERRFI1, NRIP1, and EPAS1, suggesting a role for stromal ESR1 driven endometrial pathologies. Functional assays confirmed that ESR1 promotes cell viability and, in the presence of E2, enhances migration. In this study, we reveal novel insights into ESR1-dependent transcriptional regulation using a newly developed cell culture model that restores ESR1 expression in hESCs to overcome their limited E2 responsiveness. Additionally, we demonstrate the utility of integrating HiChIP chromatin looping data with cistromic data to associate distal ESR1 binding sites to gene promoters.
Published in
Deciphering estrogen receptor alpha-driven transcription in human endometrial stromal cells via transcriptome, cistrome, and integration with chromatin landscape
Montague Redecke SG, Bell-Hensley A, Li S et al. · F&S science 2026 · PMID 40803503 · doi:10.1016/j.xfss.2025.08.002
This dataset
Open GSE295509 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE295509_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1255071 and SRA study SRP580978. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40803503) ↗
Study design
3 × NT gRNA Veh vs 3 × NT gRNA E2 vs 3 × ESR1 gRNA Veh vs 3 × ESR1 gRNA E2

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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