SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis

Szlachcic, Wojciech J.; Dąbrowska, Agnieszka; Milewska, Aleksandra; Ziojla, Natalia; Błaszczyk, Katarzyna; Barreto-Durán, Emilia; Sanak, Marek; Surmiak, Marcin; Owczarek, Katarzyna; Grzanka, Dariusz; Durzyńska, Julia; Pyrć, Krzysztof; Borowiak, Malgorzata

doi:10.1016/j.isci.2022.104594

Cited by 10 publications

(10 citation statements)

References 78 publications

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“…Moreover, immunofluorescence (IF) staining revealed the presence of ACE2 on the cell membrane of PDX1 + early pancreatic progenitor cells. 24 Hence, our findings combined with those of previous studies indicate the SARS-CoV-2 receptor ACE2 is expressed on human pancreatic progenitors and that its expression dynamically varies with the development of endocrine progenitors.…”

Section: Resultssupporting

confidence: 84%

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FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

Meng,

Liao,

et al. 2024

Sig Transduct Target Ther

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The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

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Section: Resultssupporting

confidence: 84%

“…The scRNA-seq data for endocrine progenitors (EP) cells differentiated from hPSCs demonstrated that TMPRSS2 and NRP1 were expressed in different types of progenitors. 24 …”

Section: Resultsmentioning

confidence: 99%

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

Meng,

Liao,

et al. 2024

Sig Transduct Target Ther

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“…Although primary HAE cells have gained prominence in studies of SARS-CoV-2, which is a respiratory virus, other primary cultures, such as primary human renal epithelial cells (Kohli et al, 2022), primary ocular cells (Eriksen et al, 2021preprint;Eriksen et al, 2022), human peripheral blood mononuclear cells (PBMCs) (Pontelli et al, 2022) and human pancreatic progenitors (Szlachcic et al, 2022) are permissive to SARS-CoV-2. The range of primary cells permissive to SARS-CoV-2 opens the way for in vitro studies of more complex cellular organisations, such as organoids.…”

Section: Primary Cellsmentioning

confidence: 99%

Choosing a cellular model to study SARS-CoV-2

Souza

Bideau

Boschi

et al. 2022

Front. Cell. Infect. Microbiol.

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As new pathogens emerge, new challenges must be faced. This is no different in infectious disease research, where identifying the best tools available in laboratories to conduct an investigation can, at least initially, be particularly complicated. However, in the context of an emerging virus, such as SARS-CoV-2, which was recently detected in China and has become a global threat to healthcare systems, developing models of infection and pathogenesis is urgently required. Cell-based approaches are crucial to understanding coronavirus infection biology, growth kinetics, and tropism. Usually, laboratory cell lines are the first line in experimental models to study viral pathogenicity and perform assays aimed at screening antiviral compounds which are efficient at blocking the replication of emerging viruses, saving time and resources, reducing the use of experimental animals. However, determining the ideal cell type can be challenging, especially when several researchers have to adapt their studies to specific requirements. This review strives to guide scientists who are venturing into studying SARS-CoV-2 and help them choose the right cellular models. It revisits basic concepts of virology and presents the currently available in vitro models, their advantages and disadvantages, and the known consequences of each choice.

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“…There have been two prominent theories proposed describing the mechanisms of pancreatic damage seen in SARS-CoV-2 infection, including a direct and an indirect mechanism. The direct mechanism may be explained by studies showing that pancreatic acinar, ductal, and islet cells highly express ACE2 and TMPRSS2 receptors that promote SARS-CoV-2 cell entry [225][226][227]. A study conducted by Szlachcic et al used in vitro models of human pancreatic cells to show that SARS-CoV-2 is capable of infecting and actively replicating in these cell types [226].…”

Section: Mechanisms Of Sars-cov-2 Infection In the Pancreasmentioning

confidence: 99%

“…The direct mechanism may be explained by studies showing that pancreatic acinar, ductal, and islet cells highly express ACE2 and TMPRSS2 receptors that promote SARS-CoV-2 cell entry [225][226][227]. A study conducted by Szlachcic et al used in vitro models of human pancreatic cells to show that SARS-CoV-2 is capable of infecting and actively replicating in these cell types [226]. Furthermore, Liu et al reported that in healthy individuals, the pancreas was found to express higher levels of ACE2 mRNA than in the lungs [225].…”

Section: Mechanisms Of Sars-cov-2 Infection In the Pancreasmentioning

confidence: 99%

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

Khreefa

Barbier

Koksal

et al. 2023

Cells

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The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a significant number of reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although the mechanisms of GI pathogenesis are still being examined, viral components isolated from stool samples of infected patients suggest a potential fecal–oral transmission route. In addition, viral RNA has been detected in blood samples of infected patients, making hematologic dissemination of the virus a proposed route for GI involvement. Angiotensin-converting enzyme 2 (ACE2) receptors serve as the cellular entry mechanism for the virus, and these receptors are particularly abundant throughout the GI tract, making the intestine, liver, and pancreas potential extrapulmonary sites for infection and reservoirs sites for developing mutations and new variants that contribute to the uncontrolled spread of the disease and resistance to treatments. This transmission mechanism and the dysregulation of the immune system play a significant role in the profound inflammatory and coagulative cascades that contribute to the increased severity and risk of death in several COVID-19 patients. This article reviews various potential mechanisms of gastrointestinal, liver, and pancreatic injury.

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SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis

Cited by 10 publications

References 78 publications

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

Choosing a cellular model to study SARS-CoV-2

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

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