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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; Vandana, J Jeya; 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.
Afiliación
  • Yang L; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Han Y; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Zhang T; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  • Dong X; Tianjin Institute of Health Science, Tianjin 301600, China.
  • Ge J; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Roy A; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Zhu J; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • Lu T; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
  • Vandana JJ; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • de Silva N; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
  • Robertson CC; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Xiang JZ; Columbia Center for Human Development, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Pan C; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Sun Y; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Que J; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Evans T; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Liu C; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Wang W; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Naji A; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Parker SCJ; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Schwartz RE; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
  • Chen S; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
bioRxiv ; 2024 Aug 06.
Article en En | MEDLINE | ID: mdl-39149298
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-seq analysis of human islets exposed to 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 to 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 mechanism of ß cell damage during viral exposure.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos