Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.
Cell Stem Cell
; 31(8): 1203-1221.e7, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-38878775
ABSTRACT
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 for interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides a chromatin context, which, when coupled with mouse lineage tracing, demonstrates that castration-resistant luminal cells are distinct from the pre-existent urethra-proximal stem/progenitor cells. Molecular pathway analysis and therapeutic studies further implicate AP1 (JUN/FOS), WNT/ß-catenin, FOXQ1, NF-κB, and JAK/STAT pathways as major drivers of castration-resistant luminal populations with relevance to human PCa. Our datasets, which can be explored through an interactive portal (https//visportal.roswellpark.org/data/tang/), can aid in developing combination treatments with ARSI for advanced PCa patients.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Epigênese Genética
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Análise de Célula Única
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Neoplasias de Próstata Resistentes à Castração
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2024
Tipo de documento:
Article