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Title: Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma
Authors: Sharma, 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
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Issue Date: 15-Oct-2020
Publisher: CELL PRESS
Citation: Sharma, 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.
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.
Source Title: CELL
ISSN: 10974172
DOI: 10.1016/j.cell.2020.08.040
Appears in Collections:Staff Publications

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