Novel Scalable and Simplified System to Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells

Brittany Bodnar, Yongang Zhang, Jinbiao Liu, Yuan Lin, Peng Wang, Zhengyu Wei, Sami Saribas, Yuanjun Zhu, Fang Li, Xu Wang, Wenli Yang, Qingsheng Li, Wen Zhe Ho, Wenhui Hu

Research output: Contribution to journalArticlepeer-review

Abstract

Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell types and dynamic development of MCOs and validate that these MCOs harbor microglia, astrocytes, neurons, and neural stem/progenitor cells, maturing in a manner that reflects human brain development. We introduce a novel technique for the generation of embryoid bodies (EBs) directly from induced pluripotent stem cells (iPSCs) that involves simplified steps of transitioning directly from 3D cultures as well as orbital shaking culture in a standard 6-well culture plate. This allows for the generation of MCOs with an easy-to-use system that is affordable and accessible by any general lab.

Original languageEnglish (US)
Article number682272
JournalFrontiers in Cellular Neuroscience
Volume15
DOIs
StatePublished - Jul 5 2021
Externally publishedYes

Keywords

  • cerebral organoids
  • human brain development
  • induced pluripotent stem cells
  • microglia-containing cerebral organoids
  • neural induction

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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