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Series GSE232954 Query DataSets for GSE232954
Status Public on May 24, 2024
Title Small-molecule-induced epigenetic rejuvenation overcomes myelinogenic barriers and stimulates myelin repair [HiChIP]
Organism Rattus norvegicus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Other
Summary Failure of oligodendrocytes to remyelinate underlies diseases such as multiple sclerosis (MS). We found that epigenetic silencing prevents oligodendrocytes from producing myelin sheaths in demyelinating MS lesions. Here, we developed a transgenic reporter system to identify a small-molecule epigenetic modulator that stimulates oligodendrocyte maturation and myelin ensheathment in vitro. This compound promoted remyelination in animal models of MS and myelination of regenerated axons and increased myelin sheath lengths in human iPSC-derived organoids. Multi-omics analyses revealed that the compound induced an enhancer/super-enhancer landscape that upregulates crucial myelinogenesis-associated pathways, including RRAS2-AKT signaling, driving actin depolymerization necessary for myelin ensheathment. Strikingly, the compound also induced phase-separated nuclear condensates of SREBP1/2, which concentrate transcriptional co-activators to drive lipid and cholesterol biosynthesis. Silencing expression of a potential target of the small molecule, HDAC3, facilitated robust myelination and remyelination. Our findings suggest that small-molecule-modulated epigenome rejuvenation relieves epigenetic silencing barriers and promotes myelin repair.
 
Overall design Hichip of rat iOLs treated with veh or 26C with H3K27ac antibody
 
Contributor(s) Liu X, He X, Lu QR
Citation(s) 38701782
Submission date May 19, 2023
Last update date May 24, 2024
Contact name XUEZHAO LIU
E-mail(s) xuezhao.liu@cchmc.org
Organization name cincinnati children's hospital medical center
Street address 3333 Burnet Ave. MLC 7013, T6.525
City cincinnati
State/province OH
ZIP/Postal code 45229
Country USA
 
Platforms (1)
GPL25947 Illumina NovaSeq 6000 (Rattus norvegicus)
Samples (2)
GSM7398495 rat_iOL_DMSO
GSM7398496 rat_iOL_26c
This SubSeries is part of SuperSeries:
GSE232956 Small-molecule-induced epigenetic rejuvenation overcomes myelinogenic barriers and stimulates myelin repair
Relations
BioProject PRJNA974477

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

Supplementary file Size Download File type/resource
GSE232954_RAW.tar 1.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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