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dc.titleOnco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma
dc.contributor.authorSharma, Ankur
dc.contributor.authorSeow, Justine Jia Wen
dc.contributor.authorDutertre, Charles-Antoine
dc.contributor.authorPai, Rhea
dc.contributor.authorBleriot, Camille
dc.contributor.authorMishra, Archita
dc.contributor.authorWong, Regina Men Men
dc.contributor.authorSingh, Gurmit Singh Naranjan
dc.contributor.authorSudhagar, Samydurai
dc.contributor.authorKhalilnezhad, Shabnam
dc.contributor.authorErdal, Sergio
dc.contributor.authorTeo, Hui Min
dc.contributor.authorKhalilnezhad, Ahad
dc.contributor.authorChakarov, Svetoslav
dc.contributor.authorLim, Tony Kiat Hon
dc.contributor.authorFui, Alexander Chung Yaw
dc.contributor.authorChieh, Alfred Kow Wei
dc.contributor.authorChung, Cheow Peng
dc.contributor.authorBonney, Glenn Kunnath
dc.contributor.authorGoh, Brian Kim-Poh
dc.contributor.authorChan, Jerry KY
dc.contributor.authorChow, Pierce KH
dc.contributor.authorGinhoux, Florent
dc.contributor.authorDasGupta, Ramanuj
dc.identifier.citationSharma, Ankur, Seow, Justine Jia Wen, Dutertre, Charles-Antoine, Pai, Rhea, Bleriot, Camille, Mishra, Archita, Wong, Regina Men Men, Singh, Gurmit Singh Naranjan, Sudhagar, Samydurai, Khalilnezhad, Shabnam, Erdal, Sergio, Teo, Hui Min, Khalilnezhad, Ahad, Chakarov, Svetoslav, Lim, Tony Kiat Hon, Fui, Alexander Chung Yaw, Chieh, Alfred Kow Wei, Chung, Cheow Peng, Bonney, Glenn Kunnath, Goh, Brian Kim-Poh, Chan, Jerry KY, Chow, Pierce KH, Ginhoux, Florent, DasGupta, Ramanuj (2020-10-15). Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma. CELL 183 (2) : 377-394. ScholarBank@NUS Repository.
dc.description.abstract© 2020 Elsevier Inc. We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed 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 in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease.
dc.publisherCELL PRESS
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiochemistry & Molecular Biology
dc.subjectCell Biology
dc.contributor.departmentBIOMED INST FOR GLOBAL HEALTH RES & TECH
dc.contributor.departmentDEPT OF MICROBIOLOGY & IMMUNOLOGY
dc.contributor.departmentDEPT OF OBSTETRICS & GYNAECOLOGY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
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