Innate Immunity in Pluripotent Human Cells

Hong, Xiao-Xiao; Carmichael, Gordon G.

doi:10.1074/jbc.m112.435461

Cited by 60 publications

(41 citation statements)

References 52 publications

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“…Most of the IFN-induced ISGs are antiviral genes [27]. However, several ISGs have been found to be able to promote virus replication by negatively regulating the IFN pathway [28,29]. Here we identified 477 up-regulated genes and 551 down-regulated genes in ZIKV infected cells, which include many ISGs such as OAS2, IFIT3 and IFITM1 (Figure 1).…”

Section: Discussionmentioning

confidence: 80%

2′, 5′-Oligoadenylate Synthetase 2 (OAS2) Inhibits Zika Virus Replication through Activation of Type Ι IFN Signaling Pathway

Liao

Xie

et al. 2020

Viruses

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Background: 2′, 5′-oligoadenylate synthetase 2 (OAS2) has been known as an antiviral interferon-stimulated gene (ISG). However, the role of OAS2 on Zika virus (ZIKV) replication is still unknown. In this study, we sought to explore the effect of OAS2 on ZIKV replication and its underlying mechanism. Methods: We performed RNA-Seq in A549 cells with or without ZIKV infection. OAS2 or RIG-I was overexpressed by plasmid transfection or knocked down by siRNA in A549 cells. Expression levels of mRNA and protein of selected genes were detected by RT-qPCR and Western Blot, respectively. Interferon stimulated response element (ISRE) activity was examined by dual luciferase assay. Results: We found that ZIKV infection induced OAS2 expression through a RIG-I-dependent pathway. OAS2 overexpression inhibited ZIKV replication, while OAS2 knockdown increased ZIKV replication. We observed that OAS2 inhibited ZIKV replication through enhanced IFNβ expression, leading to the activation of the Jak/STAT signaling pathway. Conclusion: ZIKV infection induced OAS2 expression, which in turn exerted its anti-ZIKV activities through the IFN-activated Jak/STAT signaling pathway.

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Section: Discussionmentioning

confidence: 80%

2′, 5′-Oligoadenylate Synthetase 2 (OAS2) Inhibits Zika Virus Replication through Activation of Type Ι IFN Signaling Pathway

Liao

Xie

et al. 2020

Viruses

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“…It has been shown that iPS cells are defective in their antiviral response as a result of downregulation of key genes involved in immune response 25 , 26 . Similarly, attenuated antiviral response reported in human embryonic stem (ES) cells is restored by differentiation, suggesting that the impaired antiviral response of iPS cells likely stemmed from the pluripotent state and might promote cell pluripotency 25 , 26 , 34 .…”

Section: Discussionmentioning

confidence: 97%

Dissecting the role of aberrant DNA methylation in human leukaemia

et al. 2015

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Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukemic clone escape and disease propagation. Here we show that, by applying cellular reprogramming to primary CML cells, aberrant DNA methylation contributes to the disease evolution. Importantly, using a BCR-ABL inducible murine model, we demonstrate that a single oncogenic lesion triggers DNA methylation changes which in turn act as a precipitating event in leukemia progression.

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“…The undifferentiated hESC and iPSC showed an attenuated type I interferon response that correspond to high expression of SOCS1, a suppressor of cytokine signaling factor (Hong and Carmichael 2013). Here, we demonstrate that the endodermal phase cells are responsive to type I IFN.…”

Section: Discussionmentioning

confidence: 99%

“…These cell types could also be exposed to infectious agents, such as pathogenic viruses and bacteria. In vitro experiments have shown that embryonic pluripotent stem cells can respond to type I (IFN-α and IFN-β) and II (IFN-γ) interferons that mediate the first line of defense against invading pathogens and generating specific immunity (Whyatt, Duwel et al 1993; Drukker, Katz et al 2002; Hong and Carmichael 2013). These observations are critical for understanding the innate immune function of pluripotent stem as well as progenitor cells and tissue rejection during cell therapy application.…”

Section: Introductionmentioning

confidence: 99%

Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection

et al. 2015

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Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long term survival of engrafting cells in the body, not only do the cells have to execute liver-specific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 post-differentiation), hepatoblast (day 15) and hepatocyte-like cells (day 21) from human embryonic stem cells (hESC). Day 5, 15 and 21 cells were stimulated with IFN-α and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-α treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFN-stimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatic cells upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs – LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival.

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Innate Immunity in Pluripotent Human Cells

Cited by 60 publications

References 52 publications

2′, 5′-Oligoadenylate Synthetase 2 (OAS2) Inhibits Zika Virus Replication through Activation of Type Ι IFN Signaling Pathway

2′, 5′-Oligoadenylate Synthetase 2 (OAS2) Inhibits Zika Virus Replication through Activation of Type Ι IFN Signaling Pathway

Dissecting the role of aberrant DNA methylation in human leukaemia

Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection

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