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Innervation of Human Intestinal Organoids
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Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P

Young Hyun Che1, In Young Choi2,3, Chan Eui Song1

  • 1Department of Biomedical science, Graduate School, Kyung Hee University, Seoul, Korea.

International Journal of Stem Cells
|June 29, 2023
PubMed
Summary

Peripheral neurons significantly influence colonic organoid development. Substance P from these neurons promotes epithelial cell maturation, offering new insights into colon development and disease modeling.

Keywords:
Colonic organoidGut developmentInter-organ crosstalkOrganogenesisPeripheral neuronPluripotent stem cell

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Area of Science:

  • Developmental Biology
  • Neuroscience
  • Gastroenterology

Background:

  • The colonic epithelium's complex cell types and differentiation mechanisms are not fully understood.
  • Colonic organoids are valuable for studying organogenesis but struggle to replicate in vivo cell configurations.
  • Investigating the role of peripheral neurons in colonic organoid formation is crucial.

Purpose of the Study:

  • To explore the biological significance of peripheral neurons in colonic organoid formation.
  • To understand the mechanisms of colonic epithelial cell differentiation.
  • To enhance organoid models for studying colon development and disease.

Main Methods:

  • Co-culturing colonic organoids with human embryonic stem cell (hESC)-derived peripheral neurons.
  • Analyzing morphological changes in epithelial cells and cell type presence.
  • Investigating the role of Substance P in epithelial cell development.

Main Results:

  • Co-culture led to morphological maturation of columnar epithelial cells in organoids.
  • Enterochromaffin cells were observed in the developed organoids.
  • Substance P, released by peripheral neurons, was identified as critical for epithelial cell development.

Conclusions:

  • Peripheral nervous system interactions are vital for colonic organoid development.
  • Peripheral neurons play a significant role in colonic epithelial cell differentiation.
  • These findings advance organoid models for organogenesis and disease research.