Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients. We identify club-like cells as a key epithelial cell subtype that acts as an interface between the prostate and the immune system. Tissue areas enriched with club-like cells have depleted androgen signaling and upregulated expression of luminal progenitor cell markers. Club-like cells display a senescence-associated secretory phenotype and their presence is linked to increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity. Our results indicate that club-like cells are associated with myeloid inflammation previously linked to androgen deprivation therapy resistance, providing a rationale for their therapeutic targeting.
from sddb import Catalog
cohort = Catalog().collection("geo-gse278936")
cohort.members # the 52 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse278936")
coll.ordered_artifacts.to_dataframe() # the 52 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse278936 --dest data/Licenses: 52 NCBI GEO policy
@article{Kiviaho_2024,
title = {Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer},
volume = {15},
ISSN = {2041-1723},
url = {http://dx.doi.org/10.1038/s41467-024-54364-1},
DOI = {10.1038/s41467-024-54364-1},
number = {1},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
author = {Kiviaho, Antti and Eerola, Sini K. and Kallio, Heini M. L. and Andersen, Maria K. and Hoikka, Miina and Tiihonen, Aliisa M. and Salonen, Iida and Spotbeen, Xander and Giesen, Alexander and Parker, Charles T. A. and Taavitsainen, Sinja and Hantula, Olli and Marttinen, Mikael and Hermelo, Ismaïl and Ismail, Mazlina and Midtbust, Elise and Wess, Maximilian and Devlies, Wout and Sharma, Abhibhav and Krossa, Sebastian and Häkkinen, Tomi and Afyounian, Ebrahim and Vandereyken, Katy and Kint, Sam and Kesseli, Juha and Tolonen, Teemu and Tammela, Teuvo L. J. and Viset, Trond and Størkersen, Øystein and Giskeødegård, Guro F. and Rye, Morten B. and Murtola, Teemu and Erickson, Andrew and Latonen, Leena and Bova, G. Steven and Mills, Ian G. and Joniau, Steven and Swinnen, Johannes V. and Voet, Thierry and Mirtti, Tuomas and Attard, Gerhardt and Claessens, Frank and Visakorpi, Tapio and Rautajoki, Kirsi J. and Tessem, May-Britt and Urbanucci, Alfonso and Nykter, Matti},
year = {2024},
month = Nov
}