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

Tomoki Kodera1, Ryosuke F Takeuchi1, Sara Takahashi1

  • 1Laboratory of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Japan.

Biochemical and Biophysical Research Communications
|April 1, 2023
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel in vitro non-human primate (NHP) cerebral model using marmoset stem cells. This model successfully recapitulates key aspects of NHP brain development and function, aiding neuroscience research.

Keywords:
Cerebral cortexInhibitory neuronsMarmosetMigrationOrganoidsSpontaneous neural activity

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Developmental Biology

Background:

  • Studying the non-human primate (NHP) brain is crucial for translating rodent research findings to human applications.
  • Current limitations exist in analyzing NHP brain at molecular, cellular, and circuit levels due to the absence of in vitro systems.

Purpose of the Study:

  • To develop a functional in vitro model of the non-human primate cerebral cortex.
  • To investigate inhibitory neuron migration and cortical network activity in this novel model.

Main Methods:

  • Generation of cerebral assembloids (CAs) by fusing cortical organoids (COs) and ganglionic eminence organoids (GEOs) derived from marmoset (Callithrix jacchus) embryonic stem cells (cjESCs).
  • Analysis of inhibitory neuron (LHX6-expressing) migration within the CAs.
  • Recording and analysis of spontaneous neural activity in COs and CAs.

Main Results:

  • LHX6-expressing inhibitory neurons successfully migrated towards the cortical side of the CAs.
  • Cortical organoids exhibited a developmental shift in neural activity from synchronized to unsynchronized patterns.
  • Cerebral assembloids, containing both excitatory and inhibitory neurons, displayed mature, unsynchronized neural network activity.

Conclusions:

  • The developed marmoset cerebral assembloid system serves as a powerful in vitro model for studying excitatory and inhibitory neuron interactions and cortical network dynamics.
  • This NHP in vitro model offers a valuable platform for advancing neurobiology research, regenerative medicine, and drug discovery, facilitating translation to human studies.