STAR Protocols (Jun 2021)

Generation and validation of APOE knockout human iPSC-derived cerebral organoids

  • Yuka A. Martens,
  • Siming Xu,
  • Richard Tait,
  • Gary Li,
  • Xinping C. Zhao,
  • Wenyan Lu,
  • Chia-Chen Liu,
  • Takahisa Kanekiyo,
  • Guojun Bu,
  • Jing Zhao

Journal volume & issue
Vol. 2, no. 2
p. 100571

Abstract

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Summary: Apolipoprotein E (apoE) is a major lipid carrier in the brain and closely associated with the pathogenesis of Alzheimer's disease (AD). Here, we describe a protocol for efficient knockout of APOE in human induced pluripotent stem cells (iPSCs) using the CRISPR-Cas9 system. We obtain homozygous APOE knockout (APOE-/-) iPSCs and further validate the deficiency of apoE in iPSC-derived cerebral organoids. APOE-/- cerebral organoids can serve as a useful tool to study apoE functions and apoE-related pathogenic mechanisms in AD.For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).

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