Dataset Information

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

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 (Spin?) 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 Spin? provide an accessible and versatile platform for modeling human brain development and disease and for compound testing, including potential ZIKV antiviral drugs.

SUBMITTER: Qian X

PROVIDER: S-EPMC4900885 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Qian Xuyu X Nguyen Ha Nam HN Song Mingxi M MM Hadiono Christopher C Ogden Sarah C SC Hammack Christy C Yao Bing B Hamersky Gregory R GR Jacob Fadi F Zhong Chun C Yoon Ki-Jun KJ Jeang William W Lin Li L Li Yujing Y Thakor Jai J Berg Daniel A DA Zhang Ce C Kang Eunchai E Chickering Michael M Nauen David D Ho Cheng-Ying CY Wen Zhexing Z Christian Kimberly M KM Shi Pei-Yong PY Maher Brady J BJ Wu Hao H Jin Peng P Tang Hengli H Song Hongjun H Ming Guo-Li GL

Cell 20160422 5

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 di ...[more]

PMID: 27118425

Similar Datasets

Project description:Background and objectiveDuring embryonic development, the dysregulation of the proliferation and differentiation of neuronal progenitors triggers congenital brain malformations. These malformations are common causes of morbidity and mortality in patients younger than 2 years old. Animal models have provided considerable insights into the etiology of diseases that cause congenital brain malformations. However, the interspecies differences in brain structure limit the ability to transfer these insights directly to studies of humans. In recent years, brain organoids generated from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) using a 3-dimensional (3D) culture system have been used to resemble the structure and function of a developing human brain. Therefore, we aimed to summarize the different congenital brain malformations that have been modeled by organoids and discuss the ability of this model to reveal the cellular and molecular mechanisms of congenital brain malformations.MethodsA comprehensive search was performed using PubMed and Web of Science's Core Collection for literature published from July 1, 2000 to July 1, 2022. Keywords included terms related to brain organoids and congenital brain malformations, as well as names of individual malformations.Key content and findingsThe self-assembled 3D aggregates have been used to recapitulate structural malformations of human brains, such as microcephaly, macrocephaly, lissencephaly (LIS), and periventricular nodular heterotopia (PH). The use of disease-specific brain organoids has revealed unprecedented details of mechanisms that cause congenital brain malformations.ConclusionsThis review summarizes the establishment and development of brain organoid technologies and provides an overview of their applications in modeling congenital brain malformations. Although several hurdles still need to be overcome, using brain organoids has greatly expanded our ability to reveal the pathogenesis of congenital brain malformations. Compared with existing methods, the combination with cutting-edge technologies enables a more accurate diagnosis and development of increasingly personalized targeted therapy for patients with congenital brain diseases.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets