Brain Region-specific Organoids using Mini-bioreactors for Modeling ZIKV Exposure

By Xuyu Qian, H. N. Nguyen, Mingxi Song, Christopher Hadiono, Sarah C. Ogden, Christy Hammack, Bing Yao, Gregory R. Hamersky, Fadi Jacob, C. Zhong and 20 more. Cell, 2016

1,925 citations recorded by the source corpus.

SUMMARY Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability and tissue heterogeneity limit their broad applications. Here we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and notably, a distinct human-specific outer radial glia cell layer. We also developed protocols for midbrain and hypothalamic organoids. Finally, we employed the forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell layer volume resembling microcephaly. Together, our brain region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human brain development and disease, and for compound testing including potential ZIKV antiviral drugs.

Subfields: Cellular and Molecular Neuroscience, Neurology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/74faef5439459aabb440d73a739abac394a26ab4

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Citations in the corpus

A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. (2019, background): “Recently, 3D organoid culture systems have been developed that capture the phenotypic and molecular heterogeneity found in various organs (Clevers, 2016), including cerebral organoids (Kadoshima et al., 2013; Lancaster et al., 2013; Paşca et al., 2015; Qian et al., 2016).”
Modeling Development and Disease with Organoids. (2016, background): “The authors propose this as a versatile experimental for mechanistic studies as well as for testing of potential ZIKV antiviral drugs (Qian et al., 2016).”
Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin producing neurons (2016, background): “These limitations have prompted the development of 3D organoid models that mimic the organization and function of brain parts using hPSCs (Lancaster et al., 2013; Mariani et al., 2015; Muguruma et al., 2015; Paşca et al., 2015; Qian et al., 2016).”
Complex oscillatory waves emerging from cortical organoids model early human brain network development (2019, background): “Organoids generated from induced pluripotent stem cells (iPSCs) have emerged as a scaled-down and three-dimensional model of the human brain, mimicking various developmental features at the cellular and molecular levels (Camp et al., 2015; Cederquist et al., 2019; Giandomenico et al., 2019; Lancaste”