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HIF-1alpha activity affects stem cell fate in patient-derived ileum organoids

GSE302327 Homo sapiens (human) Single-cell RNA-seq 29 samples Submitted 2026/01/14 Platform GPL30173
At a glance

Single-cell RNA-seq · human · 29 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
29 samples: 8 conditions, mostly with about 4 replicates eachGroups 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
Hypoxia Affects Stem Cell Fate in Patient-Derived Ileum Enteroids in a HIF-1α-Dependent MannerCells · 2025
Summary (written by the submitters)
The intestinal epithelium maintains tissue homeostasis through a dynamic balance of stem cell proliferation and differentiation along the crypt-villus axis. This process is spatially regulated, where intestinal stem cells in crypts proliferate and progenitor cells differentiate as they migrate toward the villus tips. An oxygen gradient is present along the crypt-villi structure setting the villi into a low-oxygen environment (physiological hypoxia) and the crypts into normoxia.
Read the full summary ↓
Hence, during this differentiation and migration process, intestinal epithelial cells encounter distinct oxygen microenvironments throughout their life span. Inflammatory bowel diseases and other chronic inflammatory conditions disrupt this homeostatic balance and alter local oxygen dynamics, leading to dysregulated tissue repair and regeneration. To investigate how oxygen availability influences intestinal stem cell fate, we cultured patient-derived human ileum organoids under normoxic (20% oxygen) or hypoxic (1% oxygen) conditions. Under hypoxia, organoid growth was reduced and expression of the stem cell marker OLFM4 was decreased. Bulk and single-cell RNA sequencing revealed that hypoxia suppressed Wnt signaling pathways and reduced stem cell activity. Importantly, pharmacological stabilization of HIF-1α under normoxic conditions recapitulated the hypoxia-induced loss of stemness, demonstrating that HIF-1α is a key mediator of oxygen-dependent stem cell regulation. These findings establish that physiological hypoxia in the intestinal epithelium directly regulates stem cell fate through HIF-1α stabilization, providing mechanistic insight into how oxygen availability controls intestinal homeostasis.
Published in
Hypoxia Affects Stem Cell Fate in Patient-Derived Ileum Enteroids in a HIF-1α-Dependent Manner
Uckeley ZM, Kee C, Ramirez C et al. · Cells 2025 · PMID 41511315 · doi:10.3390/cells15010031
This dataset
Open GSE302327 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 GSE302327_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1290081 and SRA study SRP600054. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41511315) ↗
Study design
8 conditions, mostly with about 4 replicates each
Ileum organoids derived from human samples un… ×4 Ileum organoids derived from human samples un… ×4 Ileum organoids derived from human samples un… ×4 Ileum organoids derived from human samples un… ×4 Ileum organoids derived from human samples un… ×4 Ileum organoids derived from human samples un… ×4 Ileum organoids derived from human samples un… ×3 Ileum organoids derived from human samples un… ×2

Supports a between-group comparison across 29 samples.

How we read this: 8 replicated groups read from 29 sample titles; they account for 29 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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