Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma (Nanostring)(Dataset ID: STDS0000068)
chevron_leftchevron_right
Catalog
Dataset information
Contributors
Accessions
How to cite
Dataset information
Summary:
Liver dysfunction is associated with diseases ranging from metabolic disorders to hepatocellular carcinomas (HCC). Here we employed single-cell RNA-sequencing to extensively characterise the cellular landscape of human liver, from development to disease. We analysed ~212,000 cells representing human fetal liver, HCC and mouse liver. Our analysis revealed a remarkable fetal-like reprogramming of the tumor microenvironment (TME). Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including the re-emergence of fetal-associated endothelial cells (PLVAP+/VEGFR2+), and fetal-like (FOLR2+) tumor-associated macrophages (TAMs). In a cross-species comparative analysis, we discovered remarkable similarity of gene expression and regulatory networks between mouse embryonically-seeded, fetal-liver and FOLR2+ tumor macrophages. Spatial transcriptomics further corroborated a shared onco-fetal ecosystem between fetal-liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem between the human fetal-liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of tumor ecosystem, provides a novel target for therapeutic interventions in HCC and also opens up avenues for identifying similar paradigms in other cancers and disease states.Overall design:
Analysis of hepatocellular carcinoma (HCC) and human fetal liver samples ,Tissue slides from 3 HCC patients (adjacent normal & tumor section for each) and 3 human fetal liver samples were used for this experiment. 12 regions of interests were selected for each of the 9 samples so a total of 108 regions of interests were analysed. The samples were stained with 96 targets (immune, stromal, epithelial and onco-fetal markers).Technology:
GeoMx DSP
Platform:
Multiplex spatial transcriptomics assay
Species:
Homo sapiens(hg38)
Tissues:
Liver
Organ parts:
Liver,Fetal liver
Submission date: 2020-08-21Update date: 2020-09-27
DOI: To be continue
Contributors
Sharma A,Seow JW,Dutertre C,Pai R,Blériot C,Mishra A,Wong RM,Singh GS,Sudhagar S,Khalilnezhad S,Erda
Contact: sharmaa@gis.a-star.edu.sg
How to cite
- Cite database of STOmicsDB:[1] Xu, Zhicheng et al. "STOmicsDB: a comprehensive database for spatial transcriptomics data sharing, analysis and visualization." Nucleic acids research vol. 52,D1 (2024): D1053-D1061. doi: 10.1093/nar/gkad933'
- Cite visualization dataset:[2] Sharma A,Seow JW,Dutertre C,Pai R,Blériot C,Mishra A,Wong RM,Singh GS,Sudhagar S,Khalilnezhad S,Erda. Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma (Nanostring)[DS/OL]. STOmicsDB, 2020[2020-08-21]. https://db.cngb.org/stomics/datasets/STDS0000068/. doi: xxxxxx#Format: {contributors}. {title}[DS/OL]. STOmicsDB, {the year of submission data}[{submission data}]. {dataset link}. doi: {doi ID}
- Cite original data article:Citation: Sharma, Ankur et al. “Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma.” Cell vol. 183,2 (2020): 377-394.e21. doi:10.1016/j.cell.2020.08.040