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Updated: Jul 5, 2025

Robust and Highly Reproducible Generation of Cortical Brain Organoids for Modelling Brain Neuronal Senescence In Vitro
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Patterning ganglionic eminences in developing human brain organoids using a morphogen-gradient-inducing device.

Narciso Pavon1, Karmen Diep2, Feiyu Yang3

  • 1Graduate Program in Neuroscience and Behavior, UMass Amherst, Amherst, MA 01003, USA; Department of Biochemistry and Molecular Biology, UMass Amherst, Amherst, MA 01003, USA.

Cell Reports Methods
|January 16, 2024
PubMed
Summary
This summary is machine-generated.

Researchers created patterned brain organoids (MIBOs) using a novel chemical gradient method. These MIBOs successfully mimic early brain development and neural activity, offering a new tool for studying neurodevelopment and diseases.

Keywords:
CP: BiotechnologyCP: Stem cellGABAergic projection neuronsbrain organoidsdiffusiondorsal-ventral axisganglionic eminenceinterneuronsmorphogen gradientpatterning

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Biotechnology

Background:

  • Early neurodevelopment relies on precise chemical signaling for tissue patterning and cell differentiation.
  • Replicating morphogen gradients in vitro is key for advanced brain models.

Purpose of the Study:

  • To develop a method for generating spatially patterned brain organoids using sustained chemical gradients.
  • To create morphogen-gradient-induced brain organoids (MIBOs) for studying neurodevelopment.

Main Methods:

  • Assembled polydimethylsiloxane devices to generate sustained chemical gradients.
  • Cultured and analyzed morphogen-gradient-induced brain organoids (MIBOs).
  • Utilized single-cell RNA sequencing for cell type analysis.

Main Results:

  • MIBOs replicated dorsal-ventral patterning of the ganglionic eminences (GE) by 3.5 weeks.
  • Single-cell RNA sequencing identified distinct GE-derived cell types, including interneurons and medium spiny neurons.
  • Long-term cultures (up to 5.5 months) showed stable neural activity.

Conclusions:

  • MIBOs provide a versatile platform for generating patterned brain organoids.
  • This method advances in vitro models for studying embryonic brain development.
  • MIBOs are suitable for modeling neurological diseases.