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Series GSE229154 Query DataSets for GSE229154
Status Public on May 05, 2023
Title Hexokinase 2-mediated gene expression via histone lactylation is required for hepatic stellate cell activation and liver fibrosis (CUT&Tag)
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Lactate was implicated in activation of hepatic stellate cells (HSCs). However, the mechanism by which lactate exerts its effect remains elusive. We show that hexokinase 2 (HK2) is sufficient to change gene expression by histone lactylation but not histone acetylation. Using RNA-seq and CUT&Tag chromatin profiling, we found that induction of HK2 expression in activated HSCs is required for the induced gene expression by elevating histone lactylation. Inhibiting histone lactylation by Hk2 deletion or pharmacological inhibition of lactate production diminishes HSC activation, whereas exogenous lactate but not acetate supplementation rescues the activation phenotype. Thus, lactate produced by activated HSCs determines the HSC fate via histone lactylation. We found that histone acetylation competes with histone lactylation, which could explain why class I HDAC inhibitors impede HSC activation. Finally, HSC-specific or systemic deletion of HK2 inhibits HSC activation and liver fibrosis in vivo. Therefore, we provide evidence that HK2 may be an effective therapeutic target for liver fibrosis.
Overall design Genomic occupancy profiling of H3K18la and H3K18ac for quiescent (QS), activated (ACT), activated HK2-deleted (KO), KO with lactate-treated (LAC) mouse primary HSCs.
Contributor(s) Hay N, Rho H
Citation(s) 37463576
Submission date Apr 06, 2023
Last update date Aug 04, 2023
Contact name Nissim Hay
Organization name University of Illinois Chicago
Department BMG
Street address 900 South Ashland Ave
City Chicago
State/province IL
ZIP/Postal code 60607
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (20)
GSM7156054 HSC_QS_H3K18la_rep1
GSM7156055 HSC_QS_H3K18la_rep2
GSM7156056 HSC_QS_H3K18ac_rep1
This SubSeries is part of SuperSeries:
GSE229156 Hexokinase 2 and lactate
BioProject PRJNA953056

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE229154_RAW.tar 892.6 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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