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Series GSE110571 Query DataSets for GSE110571
Status Public on Sep 26, 2019
Title Re-programing chromatin with a bifunctional LSD1/HDAC inhibitor induces therapeutic differentiation in DIPG [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Histone H3 lysine 27 to methionine mutations (H3K27M) resulting in aberrant chromatin regulation are frequently observed in Diffuse Intrinsic Pontine Glioma (DIPG), a pediatric brain tumor with no cure. We conducted a CRISPR screen to determine if various chromatin regulators might be targeted to treat DIPG. Excitingly, this genetic screen reveals that co-targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDACs) results in an enhanced growth suppressive effect in patient DIPG cells. Consistent with the genetic screen, a bifunctional inhibitor of HDACs and LSD1, Corin, inhibits DIPG growth in vitro and in xenografts. Mechanistically, Corin rescues H3K27me3 levels typically suppressed by the dominant effects of H3K27M mutations in DIPG and simultaneously increases HDAC-targeted H3K27ac and LSD1-targeted H3K4me1 at enhancers. Further studies reveal that Corin de-regulates DIPG transcription resulting in cell death, cell cycle arrest, and the induction of neuronal differentiation. These data suggest that co-targeting LSD1 and HDACs may represent a novel strategy for treating DIPG.
 
Overall design RNA-seq of polyA RNA from SU-DIPGXIII cells that had been treated with 0.5 uM of the LSD1 inhibitor, JKD-1-62, the HDAC inhibitor MS-275, the dual LSD1 and HDAC inhibitor, Corin, or the vehicle control, DMSO.
 
Contributor(s) Anastas J, Shi Y
Citation(s) 31631026
Submission date Feb 13, 2018
Last update date Jan 13, 2020
Contact name Jamie Anastas
E-mail(s) jamie.anastas@childrens.harvard.edu, jamieanastas@gmail.com
Phone 16174298539
Organization name Boston Children's Hospital
Department Newborn Medicine
Lab Yang Shi
Street address 300 Longwood Ave
City Boston, MA
State/province United States of America
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (12)
GSM3003393 DMSO_SUDIPGXIII_A
GSM3003394 DMSO_SUDIPGXIII_B
GSM3003395 DMSO_SUDIPGXIII_C
This SubSeries is part of SuperSeries:
GSE110572 Re-programing chromatin with a bifunctional LSD1/HDAC inhibitor induces therapeutic differentiation in DIPG
Relations
BioProject PRJNA434042
SRA SRP132895

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
GSE110571_RAW.tar 1.4 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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