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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Brainstem Organoids From Human Pluripotent Stem Cells.

Nobuyuki Eura1, Takeshi K Matsui1,2, Joachim Luginbühl3

  • 1Department of Neurology, Nara Medical University, Kashihara, Japan.

Frontiers in Neuroscience
|July 17, 2020
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Summary
This summary is machine-generated.

Researchers developed human brainstem organoids (hBSOs) to better model the brainstem. These hBSOs contain key cell types and can aid in studying brainstem disorders and drug screening.

Keywords:
brain organoidsbrainstemdopaminergic neuronshuman pluripotent stem cellsmelanocytemidbrainneural crest

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Stem Cell Research

Background:

  • The brainstem controls vital functions like heartbeat and respiration, making it crucial for life.
  • Existing human pluripotent stem cell (hPSC)-derived brain organoids do not fully recapitulate human brain development, limiting their utility for studying brainstem-specific disorders.
  • Brainstem damage or disorders can be lethal, highlighting the need for better research models.

Purpose of the Study:

  • To develop a novel method for generating human brainstem organoids (hBSOs).
  • To create organoids that accurately model the cellular composition and developmental aspects of the human brainstem.
  • To establish a valuable tool for investigating central nervous system disorders and facilitating drug discovery.

Main Methods:

  • Generation of human brainstem organoids (hBSOs) from human pluripotent stem cells (hPSCs).
  • Characterization of hBSOs using single-cell RNA sequencing (scRNA-seq).
  • Integration of proteomic and electrophysiological analyses to validate organoid fidelity.

Main Results:

  • The developed hBSOs successfully recapitulate key features of the human brainstem.
  • Organoids contain midbrain/hindbrain progenitors, noradrenergic, cholinergic, and dopaminergic neurons, and neural crest lineage cells.
  • scRNA-seq, proteomics, and electrophysiology confirmed cellular similarity to the in vivo human brainstem.

Conclusions:

  • Human brainstem organoids (hBSOs) represent a significant advancement in modeling the human brainstem.
  • hBSOs provide a powerful platform for investigating brainstem-related central nervous system disorders.
  • These organoids offer potential for efficient and effective drug screening for brainstem conditions.