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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.
  • Qian X; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Biomedical Engineering Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Nguyen HN; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Bal
  • Song MM; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Riverhill High School, Clarksville, MD 21029, USA.
  • Hadiono C; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Byram Hills High School, Armonk, NY 10504, USA.
  • Ogden SC; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
  • Hammack C; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
  • Yao B; Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Hamersky GR; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Jacob F; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Zhong C; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Yoon KJ; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Jeang W; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Clear Lake High School, Harris, TX 77058, USA.
  • Lin L; Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Li Y; Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Thakor J; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Berg DA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Zhang C; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Kang E; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Chickering M; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Nauen D; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Ho CY; Division of Pathology, Children's National Medical Center, George Washington University, Washington, DC 20010, USA; Pathology and Pediatrics, George Washington University, Washington, DC 20010, USA.
  • Wen Z; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Christian KM; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Shi PY; Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Maher BJ; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Wu H; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
  • Jin P; Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Tang H; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
  • Song H; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Bal
  • Ming GL; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Bal
Cell ; 165(5): 1238-1254, 2016 May 19.
Article en En | MEDLINE | ID: mdl-27118425
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encéfalo / Organoides / Técnicas de Cultivo de Célula / Virus Zika / Modelos Biológicos Límite: Humans Idioma: En Año: 2016 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encéfalo / Organoides / Técnicas de Cultivo de Célula / Virus Zika / Modelos Biológicos Límite: Humans Idioma: En Año: 2016 Tipo del documento: Article