Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic β cell Pyroptosis upon Viral Infection.

Autor:	Yang L; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; 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.; Tianjin Institute of Health Science, Tianjin 301600, China., Han Y; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; 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.; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China., Zhang T; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA., Dong X; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, 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 Ave, New York, NY, 10065, USA., Zhu J; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA., Lu T; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA., Vandana JJ; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA., de Silva N; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, 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 Ave, New York, NY, 10065, USA.; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA., Liu C; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA., Wang W; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA., Naji A; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 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 Ave, New York, NY, 10065, USA.; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA. New York 10021, USA., Chen S; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.; Center for Genomic Health, Weill Cornell Medicine, 1300 York Ave, New York, NY, 10065, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Aug 06. Date of Electronic Publication: 2024 Aug 06.
DOI:	10.1101/2024.08.05.606734
Abstrakt:	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 β cell pyroptosis. To distinguish viral versus proinflammatory macrophage-mediated β 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 β cells and endothelial cells compared to separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced β cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory macrophage-mediated β cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune cell-mediated host damage and uncovered mechanism of β cell damage during viral exposure. Competing Interests: DECLARATION OF INTERESTS R.E.S. is on the scientific advisory board of Miromatrix Inc. and Lime Therapeutics and is a consultant and Speaker for Alnylam Inc. S.C. and T.E are the co-founders of OncoBeat, LLC. S.C. is a consultant of Vesalius Therapeutics and co-founder of iOrganBio. The other authors have no conflict of interest.
Databáze:	MEDLINE
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