Proteomic and Transcriptional Profiles of Human Stem Cell-Derived β Cells Following Enteroviral Challenge
| Autor: | Sambra D. Redick, David M. Harlan, Natasha Qaisar, Jennifer P. Wang, Riccardo Racicot, Basanthi Satish, Pranitha Vangala, Agata Jurczyk, Julius O. Nyalwidhe, Dale L. Greiner, Melanie I. Trombly, Michael A. Brehm, Jerry L. Nadler, Rita Bortell |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) endocrine system coxsackie B virus endocrine system diseases type 1 diabetes Cell 030209 endocrinology & metabolism medicine.disease_cause Major histocompatibility complex Microbiology Article Autoimmunity Proinflammatory cytokine Transcriptome 03 medical and health sciences 0302 clinical medicine immune system diseases Interferon Virology medicine lcsh:QH301-705.5 Innate immune system biology nutritional and metabolic diseases 3. Good health Cell biology beta cells 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) biology.protein Stem cell medicine.drug |
| Zdroj: | Microorganisms Volume 8 Issue 2 Microorganisms, Vol 8, Iss 2, p 295 (2020) |
| ISSN: | 2076-2607 |
| Popis: | Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant &beta cell stress and damage occur with viral infection, leading to cells that are dysfunctional and vulnerable to destruction. Human stem cell-derived &beta (SC-&beta ) cells are insulin-producing cell clusters that closely resemble native &beta cells. To better understand the events precipitated by enteroviral infection of &beta cells, we investigated transcriptional and proteomic changes in SC-&beta cells challenged with coxsackie B virus (CVB). We confirmed infection by demonstrating that viral protein colocalized with insulin-positive SC-&beta cells by immunostaining. Transcriptome analysis showed a decrease in insulin gene expression following infection, and combined transcriptional and proteomic analysis revealed activation of innate immune pathways, including type I interferon (IFN), IFN-stimulated genes, nuclear factor-kappa B (NF-&kappa B) and downstream inflammatory cytokines, and major histocompatibility complex (MHC) class I. Finally, insulin release by CVB4-infected SC-&beta cells was impaired. These transcriptional, proteomic, and functional findings are in agreement with responses in primary human islets infected with CVB ex vivo. Human SC-&beta cells may serve as a surrogate for primary human islets in virus-induced diabetes models. Because human SC-&beta cells are more genetically tractable and accessible than primary islets, they may provide a preferred platform for investigating T1D pathogenesis and developing new treatments. |
| Databáze: | OpenAIRE |
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