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Human vascularized macrophage-islet organoids to model immune-mediated pancreatic ß cell pyroptosis upon viral infection.
Yang, Liuliu; Han, Yuling; Zhang, Tuo; Dong, Xue; Ge, Jian; Roy, Aadita; Zhu, Jiajun; Lu, Tiankun; Jeya Vandana, J; de Silva, Neranjan; Robertson, Catherine C; Xiang, Jenny Z; Pan, Chendong; Sun, Yanjie; Que, Jianwen; Evans, Todd; Liu, Chengyang; Wang, Wei; Naji, Ali; Parker, Stephen C J; Schwartz, Robert E; Chen, Shuibing.
Affiliation
  • Yang L; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Haihe Laborato
  • Han Y; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology,
  • Zhang T; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
  • Dong X; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Ge J; Columbia Center for Human Development, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Roy A; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Zhu J; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Lu T; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Jeya Vandana J; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • de Silva N; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Robertson CC; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Xiang JZ; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
  • Pan C; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
  • Sun Y; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
  • Que J; Columbia Center for Human Development, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Evans T; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Liu C; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Wang W; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Naji A; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Parker SCJ; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
  • Schwartz RE; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: res2025@med.cornell
  • Chen S; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.
Cell Stem Cell ; 2024 Aug 30.
Article in En | MEDLINE | ID: mdl-39232561
ABSTRACT
There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single-cell RNA sequencing (scRNA-seq) analysis of human islets exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and ß cell pyroptosis. To distinguish viral versus proinflammatory-macrophage-mediated ß cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both ß cells and endothelial cells compared with separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced ß cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory-macrophage-mediated ß cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune-cell-mediated host damage and uncovered the mechanism of ß cell damage during viral exposure.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Stem Cell / Cell stem cell (Online) Year: 2024 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Stem Cell / Cell stem cell (Online) Year: 2024 Document type: Article Country of publication: United States