Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure

Xuyu Qian, Ha Nam Nguyen, Mingxi M. Song, Christopher Hadiono, Sarah C. Ogden, Christy Hammack, Bing Yao, Gregory R. Hamersky, Fadi Jacob, Chun Zhong, Ki Jun Yoon, William Jeang, Li Lin, Yujing Li, Jai Thakor, Daniel A. Berg, Ce Zhang, Eunchai Kang, Michael Chickering, David Nauen & 10 others Cheng Ying Ho, Zhexing Wen, Kimberly M. Christian, Pei-Yong Shi, Brady J. Maher, Hao Wu, Peng Jin, Hengli Tang, Hongjun Song, Guo Li Ming

Research output: Contribution to journalArticle

505 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1238-1254
Number of pages17
JournalCell
Volume165
Issue number5
DOIs
StatePublished - May 19 2016

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Organoids
Bioreactors
Viruses
Brain
Human Development
Prosencephalon
Cell death
Gene expression
Antiviral Agents
Microcephaly
Organogenesis
Neurogenesis
Cells
Brain Diseases
Tissue
Mesencephalon
Cell Size
Neuroglia
Zika Virus
Testing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Qian, X., Nguyen, H. N., Song, M. M., Hadiono, C., Ogden, S. C., Hammack, C., ... Ming, G. L. (2016). Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. Cell, 165(5), 1238-1254. https://doi.org/10.1016/j.cell.2016.04.032

Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. / Qian, Xuyu; Nguyen, Ha Nam; Song, Mingxi M.; Hadiono, Christopher; Ogden, Sarah C.; Hammack, Christy; Yao, Bing; Hamersky, Gregory R.; Jacob, Fadi; Zhong, Chun; Yoon, Ki Jun; Jeang, William; Lin, Li; Li, Yujing; Thakor, Jai; Berg, Daniel A.; Zhang, Ce; Kang, Eunchai; Chickering, Michael; Nauen, David; Ho, Cheng Ying; Wen, Zhexing; Christian, Kimberly M.; Shi, Pei-Yong; Maher, Brady J.; Wu, Hao; Jin, Peng; Tang, Hengli; Song, Hongjun; Ming, Guo Li.

In: Cell, Vol. 165, No. 5, 19.05.2016, p. 1238-1254.

Research output: Contribution to journalArticle

Qian, X, Nguyen, HN, Song, MM, Hadiono, C, Ogden, SC, Hammack, C, Yao, B, Hamersky, GR, Jacob, F, Zhong, C, Yoon, KJ, Jeang, W, Lin, L, Li, Y, Thakor, J, Berg, DA, Zhang, C, Kang, E, Chickering, M, Nauen, D, Ho, CY, Wen, Z, Christian, KM, Shi, P-Y, Maher, BJ, Wu, H, Jin, P, Tang, H, Song, H & Ming, GL 2016, 'Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure', Cell, vol. 165, no. 5, pp. 1238-1254. https://doi.org/10.1016/j.cell.2016.04.032
Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C et al. Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. Cell. 2016 May 19;165(5):1238-1254. https://doi.org/10.1016/j.cell.2016.04.032
Qian, Xuyu ; Nguyen, Ha Nam ; Song, Mingxi M. ; Hadiono, Christopher ; Ogden, Sarah C. ; Hammack, Christy ; Yao, Bing ; Hamersky, Gregory R. ; Jacob, Fadi ; Zhong, Chun ; Yoon, Ki Jun ; Jeang, William ; Lin, Li ; Li, Yujing ; Thakor, Jai ; Berg, Daniel A. ; Zhang, Ce ; Kang, Eunchai ; Chickering, Michael ; Nauen, David ; Ho, Cheng Ying ; Wen, Zhexing ; Christian, Kimberly M. ; Shi, Pei-Yong ; Maher, Brady J. ; Wu, Hao ; Jin, Peng ; Tang, Hengli ; Song, Hongjun ; Ming, Guo Li. / Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. In: Cell. 2016 ; Vol. 165, No. 5. pp. 1238-1254.
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