Distinct mesenchymal cell states mediate prostate cancer progression [Spatial Transcriptomics]
import lamindb as ln
import spatialdata as sd
coll = ln.Collection.get(key="doi-10.1101/2023.03.29.534769")
coll.ordered_artifacts.df() # the 2 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]
# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()} Distinct mesenchymal cell states mediate prostate cancer progression
<h4>Summary</h4> Alterations in tumor stroma influence prostate cancer progression and metastatic potential. However, the molecular underpinnings of this stromal-epithelial crosstalk are largely unknown. Here, we compare mesenchymal cells from four genetically engineered mouse models (GEMMs) of prostate cancer representing different stages of the disease to their wild-type (WT) counterparts by single-cell RNA sequencing (scRNA-seq) and, ultimately, to human tumors with comparable genotypes. We identified 8 transcriptionally and functionally distinct stromal populations responsible for common and GEMM-specific transcriptional programs. We show that stromal responses are conserved in mouse models and human prostate cancers with the same genomic alterations. We noted striking similarities between the transcriptional profiles of the stroma of murine models of advanced disease and those of of human prostate cancer bone metastases. These profiles were then used to build a robust gene signature that can predict metastatic progression in prostate cancer patients with localized disease and is also associated with progression-free survival independent of Gleason score. Taken together, this offers new evidence that stromal microenvironment mediates prostate cancer progression, further identifying tissue-based biomarkers and potential therapeutic targets of aggressive and metastatic disease.
Cite this collection
doi.org/10.1101/2023.03.29.534769 ↗@article{Pakula_2023,
title = {Distinct mesenchymal cell states mediate prostate cancer progression},
url = {http://dx.doi.org/10.1101/2023.03.29.534769},
DOI = {10.1101/2023.03.29.534769},
publisher = {openRxiv},
author = {Pakula, Hubert and Omar, Mohamed and Carelli, Ryan and Pederzoli, Filippo and Fanelli, Giuseppe Nicolò and Pannellini, Tania and Van Emmenis, Lucie and Rodrigues, Silvia and Fidalgo-Ribeiro, Caroline and Nuzzo, Pier V. and Brady, Nicholas J. and Jere, Madhavi and Unkenholz, Caitlin and Alexanderani, Mohammad K. and Khani, Francesca and de Almeida, Francisca Nunes and Abate-Shen, Cory and Greenblatt, Matthew B and Rickman, David S. and Barbieri, Christopher E. and Robinson, Brian D. and Marchionni, Luigi and Loda, Massimo},
year = {2023},
month = Apr
}