Genetic Ablation of AXL Does Not Protect Human Neural Progenitor Cells and Cerebral Organoids from Zika Virus Infection

Wells, Michael F.; Salick, Max R.; Wiskow, Ole; Ho, Daniel J.; Worringer, Kathleen A.; Ihry, Robert J.; Kommineni, Sravya; Bilican, Bilada; Klim, Joseph R.; Hill, Ellen J.; Kane, Liam T.; Ye, Chaoyang; Kaykas, Ajamete; Eggan, Kevin

doi:10.1016/j.stem.2016.11.011

Cited by 235 publications

(201 citation statements)

References 27 publications

(23 reference statements)

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“…A number of studies have since modeled ZIKV infection using human NPC monolayer and neurosphere cultures, acute fetal brain slices, and brain organoids (Barrows et al, 2016;Cugola et al, 2016;Dang et al, 2016;Garcez et al, 2016;Hanners et al, 2016;Liang et al, 2016;Onorati et al, 2016;Qian et al, 2016;Retallack et al, 2016;Simonin et al, 2016;Wells et al, 2016) (Fig. 1).…”

Section: Using Brain Organoids To Study Zikv-induced Microcephalymentioning

confidence: 99%

“…Moreover, owing to the long-term nature of organoid culturing, small perturbations in culture conditions could potentially change the outcome significantly. While efforts have been made to generate brain region-specific organoids under defined conditions, it is important to establish common standards of organoid quality by carefully characterizing multiple aspects, including lineage Barrows et al, 2016;Garcez et al, 2016;Hanners et al, 2016;Onorati et al, 2016;Simonin et al, 2016;Tang et al, 2016;Wells et al, 2016;Xu et al, 2016;Zhang et al, 2016 Fig. 1.…”

Section: Limitations Of Current Brain Organoid Systems For Zikv Researchmentioning

confidence: 99%

“…For example, the observation that the AXL receptor tyrosine kinase protein is highly expressed in human RGCs and oRGCs has led to the hypothesis that it could function as a ZIKV entry receptor in NPCs (Nowakowski et al, 2016a). To test this hypothesis, AXL was deleted via genome editing in hPSCs and the resulting cerebral organoids showed no difference in ZIKV infection and pathophysiology, suggesting that AXL is dispensable for ZIKV infection in human NPCs (Wells et al, 2016). In another example, a recent study screened over 6000 drug candidates and approved drugs using monolayer NPC cultures and identified a number of hits that were then applied to forebrain organoids to test drug efficacy and to evaluate potential toxicity .…”

Section: Using Brain Organoids For Zikv Research: the Next Phasementioning

confidence: 99%

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Using brain organoids to understand Zika virus-induced microcephaly

et al. 2017

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Technologies to differentiate human pluripotent stem cells into threedimensional organized structures that resemble in vivo organs are pushing the frontiers of human disease modeling and drug development. In response to the global health emergency posed by the Zika virus (ZIKV) outbreak, brain organoids engineered to mimic the developing human fetal brain have been employed to model ZIKV-induced microcephaly. Here, we discuss the advantages of brain organoids over other model systems to study development and highlight recent advances in understanding ZIKV pathophysiology and its underlying pathogenesis mechanisms. We further discuss perspectives on overcoming limitations of current organoid systems for their future use in ZIKV research.

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Section: Using Brain Organoids To Study Zikv-induced Microcephalymentioning

confidence: 99%

Section: Limitations Of Current Brain Organoid Systems For Zikv Researchmentioning

confidence: 99%

Section: Using Brain Organoids For Zikv Research: the Next Phasementioning

confidence: 99%

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Using brain organoids to understand Zika virus-induced microcephaly

et al. 2017

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“…ZIKV can bind to target cells using adhesion factors such as DC-SIGN and phosphatidylserine binding receptors (Hamel et al, 2017) from which Axl appeared as the main receptor for the entry in human skin fibroblasts (Hamel et al, 2015), microglia (Meertens et al, 2017), astrocytes (Retallack et al, 2016;Meertens et al, 2017) and blood-brain barrier endothelial cells . Surprisingly, Axl does not seem to be necessary for the entry of ZIKV in NPC and cerebral organoids (Wells et al, 2016;Meertens et al, 2017), despite the high expression of this receptor in NSC and NPC (Cugola et al, 2016;Liu et al, 2016;Nowakowski et al, 2016;Onorati et al, 2016;Meertens et al, 2017). Replication and assembly of progeny virions of ZIKV take place onto modified membranes derived from the endoplasmic reticulum.…”

Section: Mechanisms Of Zikv Entry In Human Cells and The Antiviral Rementioning

confidence: 98%

“…Studies using an Asian strain of ZIKV (FSS13025, isolated in Cambodia) or ZIKV isolated from recent outbreaks in Brazil (Cugola et al, 2016;Souza et al, 2016;Garcez et al, 2017;Sacramento et al, 2017), Puerto Rico (Hanners et al, 2016;Wells et al, 2016) and French Polynesia (Ghouzzi et al, 2016) have shown the ability of the virus to infect and induce apoptosis of human NPC.…”

Section: Zikv Induces Apoptosis Autophagy and Mitotic Abnormalities mentioning

confidence: 99%

Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic?

2018

Frontiers Research Topics

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Zika is a viral disease transmitted mainly by mosquitoes of the genus Aedes. In recent years, it has expanded geographically, changing from an endemic mosquito-borne disease across equatorial Asia and Africa, to an epidemic disease causing large outbreaks in several areas of the world. With the recent Zika virus (ZIKV) outbreaks in the Americas, the disease has become a focus of attention of public health agencies and of the international research community, especially due to an association with neurological disorders in adults and to the severe neurological and ophthalmological abnormalities found in fetuses and newborns of mothers exposed to ZIKV during pregnancy. A large number of studies have been published in the last 3 years, revealing the structure of the virus, how it is transmitted and how it affects human cells. Many different animal models have been developed, which recapitulate several features of ZIKV disease and its neurological consequences. Moreover, several vaccine candidates are now in active preclinical development, and three of them have already entered phase I clinical trials. Likewise, many different compounds targeting viral and cellular components are being tested in in vitro and in experimental animal models. This review aims to discuss the current state of this rapidly growing literature from a multidisciplinary perspective, as well as to present an overview of the public health response to Zika and of the perspectives for the prevention and treatment of this disease.

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Innovations in 3D Tissue Models of Human Brain Physiology and Diseases

Lovett

Nieland

Dingle

et al. 2020

Adv Funct Materials

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3D laboratory tissue cultures have emerged as an alternative to traditional 2D culture systems that do not recapitulate native cell behavior. The discrepancy between in vivo and in vitro tissue-cell-molecular responses impedes understanding of human physiology in general and creates roadblocks for the discovery of therapeutic solutions. Two parallel approaches have emerged for the design of 3D culture systems. The first is biomedical engineering methodology, including bioengineered materials, bioprinting, microfluidics, and bioreactors, used alone or in combination, to mimic the microenvironments of native tissues. The second approach is organoid technology, in which stem cells are exposed to chemical and/or biological cues to activate differentiation programs that are reminiscent of human (prenatal) development. This review article describes recent technological advances in engineering 3D cultures that more closely resemble the human brain. The contributions of in vitro 3D tissue culture systems to new insights in neurophysiology, neurological diseases, and regenerative medicine are highlighted. Perspectives on designing improved tissue models of the human brain are offered, focusing on an integrative approach merging biomedical engineering tools with organoid biology.

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Genetic Ablation of AXL Does Not Protect Human Neural Progenitor Cells and Cerebral Organoids from Zika Virus Infection

Cited by 235 publications

References 27 publications

Using brain organoids to understand Zika virus-induced microcephaly

Using brain organoids to understand Zika virus-induced microcephaly

Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic?

Innovations in 3D Tissue Models of Human Brain Physiology and Diseases

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