Tumour-like druggable gene expression pattern of CaCo2 cells in microfluidic chip

Samatov, Timur R.; Senyavina, N. V.; Galatenko, Vladimir; Trushkin, E. V.; Tonevitskaya, S. A.; Alexandrov, Dmitriy E.; Shibukhova, Galina P.; Schumacher, Udo; Tonevitsky, Alexander G.

doi:10.1007/s13206-016-0308-3

Cited by 23 publications

(5 citation statements)

References 13 publications

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“…During long-term cultivation, Caco-2 cells polarize, form microvilli, tight junctions, extracellular matrix, and begin to express specific enterocyte markers (146)(147)(148). Models based on Caco-2 cells using microfluidic devices that create medium flow make the model even closer to the physiological conditions of human intestine (149)(150)(151). The lung-on-chip model in a microfluidic device can be used to study influenza A virus cell entry, replication, virulence of different strains, cytokine production by host cells, and circulating immune cell recruitment (152).…”

Section: Using Tissue Barrier Models To Study Coronavirus Transcytosismentioning

confidence: 99%

“…We previously published the results of a transcriptome study using Affymetrix Human Gene 1.0 ST Arrays (GSE81867) for Caco-2 cells grown either on Transwell culture inserts in static medium or on a microfluidic chip with culture medium circulation ( 150 , 151 ). Further transcriptome analyses revealed high FCGRT gene expression in differentiated Caco-2 for both conditions.…”

Section: Using Tissue Barrier Models To Study Coronavirus Transcytosismentioning

confidence: 99%

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Endocytosis and Transcytosis of SARS-CoV-2 Across the Intestinal Epithelium and Other Tissue Barriers

2021

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Since 2003, the world has been confronted with three new betacoronaviruses that cause human respiratory infections: SARS-CoV, which causes severe acute respiratory syndrome (SARS), MERS-CoV, which causes Middle East respiratory syndrome (MERS), and SARS-CoV-2, which causes Coronavirus Disease 2019 (COVID-19). The mechanisms of coronavirus transmission and dissemination in the human body determine the diagnostic and therapeutic strategies. An important problem is the possibility that viral particles overcome tissue barriers such as the intestine, respiratory tract, blood-brain barrier, and placenta. In this work, we will 1) consider the issue of endocytosis and the possibility of transcytosis and paracellular trafficking of coronaviruses across tissue barriers with an emphasis on the intestinal epithelium; 2) discuss the possibility of antibody-mediated transcytosis of opsonized viruses due to complexes of immunoglobulins with their receptors; 3) assess the possibility of the virus transfer into extracellular vesicles during intracellular transport; and 4) describe the clinical significance of these processes. Models of the intestinal epithelium and other barrier tissues for in vitro transcytosis studies will also be briefly characterized.

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Section: Using Tissue Barrier Models To Study Coronavirus Transcytosismentioning

confidence: 99%

Section: Using Tissue Barrier Models To Study Coronavirus Transcytosismentioning

confidence: 99%

Endocytosis and Transcytosis of SARS-CoV-2 Across the Intestinal Epithelium and Other Tissue Barriers

2021

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“…Extracellular matrix can support cell attachment, proliferation, and differentiation ( Mutsenko et al, 2017 ), and use of laminins specific for the intestinal basal membrane can bring the gut model properties closer to conditions in vivo ( Nikulin et al, 2018a , 2019 ). Microfluidic devices with a culture medium flow that simulates blood flow create even more physiological conditions for the cell model ( Samatov et al, 2016 , 2017 ; Sakharov et al, 2019 ). Caco-2 intestinal model is suitable to study hypoxia effects ( Maltseva et al, 2020 ; Nersisyan et al, 2021a ).…”

Section: Introductionmentioning

confidence: 99%

HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease

et al. 2021

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Intestinal epithelial cells exist in physiological hypoxia, leading to hypoxia-inducible factor (HIF) activation and supporting barrier function and cell metabolism of the intestinal epithelium. In contrast, pathological hypoxia is a common feature of some chronic disorders, including inflammatory bowel disease (IBD). This work was aimed at studying HIF-associated changes in the intestinal epithelium in IBD. In the first step, a list of genes responding to chemical activation of hypoxia was obtained in an in vitro intestinal cell model with RNA sequencing. Cobalt (II) chloride and oxyquinoline treatment of both undifferentiated and differentiated Caco-2 cells activate the HIF-signaling pathway according to gene set enrichment analysis. The core gene set responding to chemical hypoxia stimulation in the intestinal model included 115 upregulated and 69 downregulated genes. Of this set, protein product was detected for 32 genes, and fold changes in proteome and RNA sequencing significantly correlate. Analysis of publicly available RNA sequencing set of the intestinal epithelial cells of patients with IBD confirmed HIF-1 signaling pathway activation in sigmoid colon of patients with ulcerative colitis and terminal ileum of patients with Crohn’s disease. Of the core gene set from the gut hypoxia model, expression activation of ITGA5 and PLAUR genes encoding integrin α5 and urokinase-type plasminogen activator receptor (uPAR) was detected in IBD specimens. The interaction of these molecules can activate cell migration and regenerative processes in the epithelium. Transcription factor analysis with the previously developed miRGTF tool revealed the possible role of HIF1A and NFATC1 in the regulation of ITGA5 and PLAUR gene expression. Detected genes can serve as markers of IBD progression and intestinal hypoxia.

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“…It is of great value to monitor the cardiac differentiation in vitro since the pathogenesis of some cardiomyopathies and congenital heart diseases could be recapitulated via this process. − Besides issues with complexity and exorbitant costs, existing biosensors for monitoring cardiac differentiation in vitro have been reported to inevitably affect the biological process of differentiation through altering gene expression profiles, and thus differentiation and maturation are largely studied by performing single-cell or bulk RNA extractions and sequencing, which incur cell damage/death. , According to our previous study, the microgroove structural color GelMA films could change color in real time due to the different external forces which could actuate the films to deform and/or bend, providing insights to maturation without a need to kill cells . We next hypothesize that the color varieties of the microgroove structural color GelMA films could be utilized to monitor the cardiac differentiation process in real time, and by correlating gene expression profiles with structural color spectral data through statistical models, we could apprehend the changes in gene expression during differentiation just by monitoring color.…”

mentioning

confidence: 99%

Intrinsic Color Sensing System Allows for Real-Time Observable Functional Changes on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Gong

et al. 2020

ACS Nano

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Stem-cell based in vitro differentiation for disease modeling offers great value to explore the molecular and functional underpinnings driving many types of cardiomyopathy and congenital heart diseases. Nevertheless, one major caveat in the application of in vitro differentiation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) involves the immature phenotype of the CMs. Most of the existing methods need complex apparatus and require laborious procedures in order to monitor the cardiac differentiation/maturation process and often result in cell death. Here we developed an intrinsic color sensing system utilizing a microgroove structural color methacrylated gelatin film, which allows us to monitor the cardiac differentiation process of hiPSC-derived cardiac progenitor cells in real time. Subsequently this system can be employed as an assay system to live monitor induced functional changes on hiPSC-CMs stemming from drug treatment, the effects of which are simply revealed through color diversity. Our research shows that early intervention of cardiac differentiation through simple physical cues can enhance cardiac differentiation and maturation to some extent. Our system also simplifies the previous complex experimental processes for evaluating the physiological effects of successful differentiation and drug treatment and lays a solid foundation for future transformational applications.

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Tumour-like druggable gene expression pattern of CaCo2 cells in microfluidic chip

Cited by 23 publications

References 13 publications

Endocytosis and Transcytosis of SARS-CoV-2 Across the Intestinal Epithelium and Other Tissue Barriers

Endocytosis and Transcytosis of SARS-CoV-2 Across the Intestinal Epithelium and Other Tissue Barriers

HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease

Intrinsic Color Sensing System Allows for Real-Time Observable Functional Changes on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

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