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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 14, 2024 |
| Title |
Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells (scRNA-seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Understanding prostate response to castration and androgen receptor signaling inhibitors (ARSI) is critical to improving long-term prostate cancer (PCa) patient survival. Here we use a multi-omics approach on 229,794 single cells to create a mouse single-cell reference atlas better suited to interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides chromatin context, which, when coupled with mouse lineage tracing demonstrates that the castration-resistant luminal cells are distinct from the pre-existent urethra-proximal stem/progenitor cells. Molecular pathway analysis and therapeutic studies further implicate JUN/FOS, WNT/b-Catenin, FOXQ1, NFkB, and JAK/STAT pathways as the major drivers of castration-resistant luminal populations with high relevance to human PCa. Importantly, we demonstrate the utility of our datasets, which can be explored through an interactive portal (https://visportal.roswellpark.org/data/tang/), to aid in developing novel combination treatments with ARSI for advanced PCa patients.
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| Overall design |
Prostates from C57Bl/6 wild type mice were collected from intact, castrate, and testosterone regenerated mice at 12 weeks of age. Mice were castrated for 4 weeks and regenerated for 96 hours with testosterone pellets. Prostates were digested into single cells and analyzed using scRNAseq and scATACseq to understand prostate cell response to castration and regeneration.
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| Contributor(s) |
Kirk JS, Wang J, Tracz A, Long M, Rosario S, Ji Y, Kumar R, Liu X, Singh PK, Puzanov I, Chatta G, Cheng Q, Huang J, Wrana JL, Lovell J, Yu H, Liu S, Shen MM, Liu T, Tang DG |
| Citation(s) |
38878775 |
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| Submission date |
Mar 10, 2023 |
| Last update date |
Sep 13, 2024 |
| Contact name |
Tao Liu |
| E-mail(s) |
tao.liu@roswellpark.org
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| Phone |
7168451300
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| Organization name |
Roswell Park Comprehensive Cancer Institute
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| Department |
Biostatistics and Bioinformatics
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| Street address |
Elm and Carlton St
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| City |
Buffalo |
| State/province |
NY |
| ZIP/Postal code |
14263 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (18)
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| GSM7091758 |
AP1-Castrated, replicate 2, scRNA |
| GSM7091759 |
DLVP-Intact, replicate 1, scRNA |
| GSM7091760 |
DLVP-Intact, replicate 2, scRNA |
| GSM7091761 |
DLVP-Intact, replicate 3, scRNA |
| GSM7091762 |
DLVP-Intact, replicate 4, scRNA |
| GSM7091763 |
DLVP-Castrated, replicate 1, scRNA |
| GSM7091764 |
DLVP-Castrated, replicate 2, scRNA |
| GSM7091765 |
DLVP-Castrated, replicate 3, scRNA |
| GSM7091766 |
DLVP-Castrated, replicate 4, scRNA |
| GSM7091767 |
AP2-Intact, replicate 1, scRNA |
| GSM7091768 |
AP2-Intact, replicate 2, scRNA |
| GSM7091769 |
AP2-Castrated, replicate 1, scRNA |
| GSM7091770 |
AP2-Castrated, replicate 2, scRNA |
| GSM7091771 |
AP2-Regenerated, replicate 1, scRNA |
| GSM7091772 |
AP2-Regenerated, replicate 2, scRNA |
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| This SubSeries is part of SuperSeries: |
| GSE227109 |
Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells. |
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| Relations |
| BioProject |
PRJNA943237 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE227108_RAW.tar |
1.7 Gb |
(http)(custom) |
TAR (of H5) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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