GEO series
Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes [RNA-seq]
GSE287688
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
68 samples
Submitted 2026/02/19
Platform GPL34290Platform GPL34284Platform GPL13112
Summary
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. 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
Chen L, Kang Z, Härdfeldt J et al.
· Nature communications 2026
· PMID 41872164
· doi:10.1038/s41467-026-70846-w
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE287688_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 68 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1214249 and SRA study SRP559171. Searching any of these in the dataset finder brings you back here.
Study design
6 conditions, mostly with about 4 replicates each
Male_WT ×5
Male_LKO ×5
HRO_NC ×4
HRO_KDM6A_knockdown ×4
HRO_HNF4A_knockdown ×4
Female_WT ×2
huh7_siLuc_rep1(KAKD group) ×1
huh7_siLuc_rep2(KAKD group) ×1
+14 more
Supports a between-group comparison across 24 samples.
6 replicated groups read from the first 40 of 68 sample titles; they account for 24 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8749866 HRO_NC_rep1
- GSM8749867 HRO_NC_rep2
- GSM8749868 HRO_NC_rep3
- GSM8749869 HRO_NC_rep4
- GSM8749870 HRO_KDM6A_knockdown_rep1
- GSM8749871 HRO_KDM6A_knockdown_rep2
- GSM8749872 HRO_KDM6A_knockdown_rep3
- GSM8749873 HRO_KDM6A_knockdown_rep4
- GSM8749874 HRO_HNF4A_knockdown_rep1
- GSM8749875 HRO_HNF4A_knockdown_rep2
- GSM8749876 HRO_HNF4A_knockdown_rep3
- GSM8749877 HRO_HNF4A_knockdown_rep4
- GSM8749878 huh7_siLuc_rep1(KAKD group)
- GSM8749879 huh7_siLuc_rep2(KAKD group)
- GSM8749880 huh7_siLuc_rep3(KAKD group)
- GSM8749881 huh7_siLuc_rep4(KAKD group)
- GSM8749882 huh7_siKDM6A_rep1(KAKD group)
- GSM8749883 huh7_siKDM6A_rep2(KAKD group)
- GSM8749884 huh7_siKDM6A_rep3(KAKD group)
- GSM8749885 huh7_siKDM6A_rep4(KAKD group)
- GSM8749886 huh7_siLuc_rep1(HAKD group)
- GSM8749887 huh7_siLuc_rep2(HAKD group)
- GSM8749888 huh7_siLuc_rep3(HAKD group)
- GSM8749889 huh7_siLuc_rep4(HAKD group)
- GSM8749890 huh7_siHNF4A_rep1(HAKD group)
- GSM8749891 huh7_siHNF4A_rep2(HAKD group)
- GSM8749892 huh7_siHNF4A_rep3(HAKD group)
- GSM8749893 huh7_siHNF4A_rep4(HAKD group)
- GSM8749894 Male_WT_rep1
- GSM8749895 Male_WT_rep2
- GSM8749896 Male_WT_rep3
- GSM8749897 Male_WT_rep4
- GSM8749898 Male_WT_rep5
- GSM8749899 Male_LKO_rep1
- GSM8749900 Male_LKO_rep2
- GSM8749901 Male_LKO_rep3
- GSM8749902 Male_LKO_rep4
- GSM8749903 Male_LKO_rep5
- GSM8749904 Female_WT_rep1
- GSM8749905 Female_WT_rep2
+ 28 more — browse all 68 samples with per-sample file links →
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