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Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes [RNA-seq]

GSE287688 Homo sapiens (human) RNA-seq (gene expression) 68 samples Submitted 2026/02/19 Platform GPL34290Platform GPL34284Platform GPL13112
At a glance

RNA-seq (gene expression) · human · 68 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
68 samples: 12 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
Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytesNature communications · 2026
Summary (written by the submitters)
The liver is a central organ controlling lipid and cholesterol metabolism and plays a key role in regulating lipoprotein profiles and cardiovascular disease risk. Males and females show clear differences in cholesterol handling and susceptibility to atherosclerosis, but the molecular basis for these sex-specific effects remains incompletely understood.
Read the full summary ↓
Here we show that the X-linked histone demethylase 6A (KDM6A) is essential for maintaining healthy cholesterol metabolism in the liver. Reducing KDM6A levels in human liver cells disrupts gene programs involved in lipoprotein regulation linked to cardiovascular disorders. Consistently, female mice lacking KDM6A specifically in hepatocytes develops pro-atherogenic blood lipoprotein profiles and increased atherosclerosis under genetic and dietary stress, whereas males are largely unaffected. Mechanistically, KDM6A cooperates with Hepatocyte Nuclear Factor 4 Alpha (HNF4A) to promote chromatin activation and enable CREBH (encoded by CREB3L3)-dependent transcription of lipid metabolic genes. These findings identify KDM6A as a sex-linked regulator of hepatic cholesterol metabolism.
Published in
Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes
Chen L, Kang Z, Härdfeldt J et al. · Nature communications 2026 · PMID 41872164 · doi:10.1038/s41467-026-70846-w
This dataset
Open GSE287688 in finder → Find more 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 GSE287688_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 PRJNA1214249 and SRA study SRP559171. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41872164) ↗
Study design
12 conditions, mostly with about 4 replicates each
Male_WT ×5 Male_LKO ×5 Female_WT ×5 Female_LKO ×5 HRO_NC ×4 HRO_KDM6A_knockdown ×4 HRO_HNF4A_knockdown ×4 Huh1_siLuc ×4 +20 more

Supports a between-group comparison across 52 samples.

How we read this: 12 replicated groups read from 68 sample titles; they account for 52 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

+ 28 more — browse all 68 samples with per-sample file links →

Datasets on a similar topic

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