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Series GSE183196 Query DataSets for GSE183196
Status Public on Mar 30, 2022
Title ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [ATAC-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Treatment with androgen receptor pathway inhibitors (ARPIs) in prostate cancer leads to the emergence of resistant tumors characterized by lineage plasticity and divergent differentiation toward neuroendocrine lineage. We found that ARPIs induce a rapid epigenetic alteration mediated by large-scale chromatin remodeling to support activation of stem/neuronal transcriptional programs. We identified motifs for the proneuronal transcription factor ASCL1 to be enriched in hyper-accessible regions. ASCL1 acts as a driver of the lineage plastic, neuronal transcriptional program to support treatment resistance and neuroendocrine phenotype. Targeting ASCL1 switches the neuroendocrine lineage back to the luminal epithelial state. This effect is modulated by disruption of the polycomb repressive complex-2 and change the chromatin architecture in favor of luminal phenotype. Our study provides insights into the epigenetic alterations induced by ARPI governed by ASCL1, provides a proof of principle of targeting ASCL1 to reverse the neuroendocrine phenotype, support luminal conversion and re-addiction to ARPIs.
 
Overall design Deciphering enzalutamide dependent prostate cancer stage specific chromatin accessibility profile.
 
Contributor(s) Nouruzi S, Ganguli D, Tabrizian N, Kobelev M, Sivak O, Namekawa T, Aguda A, Thaper D, Davies A, Zoubeidi A
Citation(s) 35477723
Submission date Sep 01, 2021
Last update date May 05, 2022
Contact name Amina Zoubeidi
E-mail(s) azoubeidi@prostatecentre.com
Organization name Vancouver Prostate Centre
Street address 2660 Oak Street
City Vancouver
State/province BC
ZIP/Postal code V6H 3Z6
Country Canada
 
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM5553084 16D-CRPC-0d-ENZ-ATAC
GSM5553085 16D-CRPC-3d-ENZ-ATAC
GSM5553086 16D-CRPC-10d-ENZ-ATAC
This SubSeries is part of SuperSeries:
GSE183200 ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer
Relations
BioProject PRJNA759599
SRA SRP335216

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
GSE183196_RAW.tar 2.7 Gb (http)(custom) TAR (of BW, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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