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Series GSE267982 Query DataSets for GSE267982
Status Public on May 21, 2024
Title ​​​​In vivo interaction screening reveals liver-derived constraints to metastasis [Single Cell Multiome ATAC + Gene Expression]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary It is estimated that only 0.02% of disseminated tumor cells are able to seed overt metastases1. While this suggests the presence of environmental constraints to metastatic seeding, the landscape of host factors controlling this process remains largely unknown. Combining transposon technology2 and fluorescent niche labeling3, we developed an in vivo CRISPR activation screen to systematically investigate the interactions between hepatocytes and metastatic cells. Our approach enabled the identification of Plexin B2 as a critical host-derived regulator of liver colonization in colorectal, pancreatic cancer and melanoma syngeneic mouse models. We dissect a mechanism by which Plexin B2 interacts with class IV semaphorins on tumor cells, leading to Klf4 upregulation and thereby promoting the acquisition of epithelial traits. Our findings highlight the essential role of signals from the liver parenchyma for the seeding of disseminated tumor cells, prior to the establishment of a growth promoting niche. They further suggest that epithelialization is required for the adaptation of CRC metastases to their new tissue environment. Blocking the Plexin B2-semaphorin axis abolishes metastatic colonization of the liver and thus represents a new therapeutic strategy for the prevention of hepatic metastases. Finally, our screening approach, which evaluates host-derived extrinsic signals rather than tumor-intrinsic factors for their ability to promote metastatic seeding, is broadly applicable and lays a framework for the screening of environmental constraints to metastasis in other organs and cancer types.
Overall design Single-cell RNA sequencing (10x) of AKPS organoids treated with recombinant mouse Plexin B2 or vehicle
Contributor(s) Borrelli C, Moor A
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Submission date May 21, 2024
Last update date May 22, 2024
Contact name Costanza Borrelli
Organization name ETH Zurich
Street address Mattenstrasse 26
City Basel
ZIP/Postal code 4028
Country Switzerland
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM8282886 AKPS in PlexinB2 OE, RNA, replicate 1
GSM8282887 AKPS in PlexinB2 OE, ATAC, replicate 1
GSM8282888 AKPS in sgNT, RNA, replicate 1
BioProject PRJNA1113988

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Supplementary file Size Download File type/resource
GSE267982_RAW.tar 8.4 Gb (http)(custom) TAR (of BED, CSV, H5, MTX, TSV)
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Raw data are available in SRA

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