Modeling the marmoset brain using embryonic stem cell-derived cerebral assembloids

Tomoki Kodera, Ryosuke F. Takeuchi, Sara Takahashi, Keiichiro Suzuki, Hidetoshi Kassai, Atsu Aiba, Seiji Shiozawa, Hideyuki Okano, Fumitaka Osakada

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Studying the non-human primate (NHP) brain is required for the translation of rodent research to humans, but remains a challenge for molecular, cellular, and circuit-level analyses in the NHP brain due to the lack of in vitro NHP brain system. Here, we report an in vitro NHP cerebral model using marmoset (Callithrix jacchus) embryonic stem cell-derived cerebral assembloids (CAs) that recapitulate inhibitory neuron migration and cortical network activity. Cortical organoids (COs) and ganglionic eminence organoids (GEOs) were induced from cjESCs and fused to generate CAs. GEO cells expressing the inhibitory neuron marker LHX6 migrated toward the cortical side of CAs. COs developed their spontaneous neural activity from a synchronized pattern to an unsynchronized pattern as COs matured. CAs containing excitatory and inhibitory neurons showed mature neural activity with an unsynchronized pattern. The CAs represent a powerful in vitro model for studying excitatory and inhibitory neuron interactions, cortical dynamics, and their dysfunction. The marmoset assembloid system will provide an in vitro platform for the NHP neurobiology and facilitate translation into humans in neuroscience research, regenerative medicine, and drug discovery.

Original languageEnglish
Pages (from-to)119-127
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume657
DOIs
Publication statusPublished - 2023 May 21

Keywords

  • Cerebral cortex
  • Inhibitory neurons
  • Marmoset
  • Migration
  • Organoids
  • Spontaneous neural activity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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