from sddb import Catalog
cohort = Catalog().collection("geo-gse262162")
cohort.members # the 2 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-gse262162")
coll.ordered_artifacts.to_dataframe() # the 2 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-gse262162 --dest data/Licenses: 2 NCBI GEO policy
Cholangiocarcinoma (CCA) is an adenocarcinoma of the hepatobiliary system that has recently risen in incidence and mortality with unsatisfactory treatment options. Claudin-1 (CLDN1) is a transmembrane protein expressed in tight junctions and exposed on the cell surface in liver fibrosis and cancer. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics of tissues of patients with CCA, we show that CLDN1 expression is up-regulated in cancer cells and is associated with stemness and cell fate. Genetic gain-of-function studies in CCA orthotopic in vivo mouse models showed decreased survival and enhanced tumor growth, unraveling a functional role of CLDN1 as an oncogenic driver. Targeting exposed nonjunctional CLDN1 using highly specific CLDN1 monoclonal antibodies (mAbs) inhibited tumor growth across CCA CDX and PDX mouse models and patient-derived CCA organoids, including tumors with medium or low CLDN1 expression. Moreover, antibody treatment inhibited tumor cell migration, invasion, and extrahepatic metastasis. Mechanistically, targeting exposed cell surface CLDN1 on CCA tumors using mAbs inhibited Notch1 and TROP2/STAT3 signaling pathways, resulting in decreased cancer cell stemness and epithelial-to-mesenchymal transition. Loss-of-function studies using CRISPR-Cas9 and RNAi combined with rescue and confocal imaging studies confirmed the functional and mechanistic role of these pathways. In conclusion, these results uncover CLDN1 as a previously undiscovered CCA driver and therapeutic target, paving the way for the clinical development of CLDN1 mAbs to improve the dismal outcome of patients with advanced CCA.
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