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Generating Enteric Nervous System Progenitors from Human Pluripotent Stem Cells.

Antigoni Gogolou1, Thomas J R Frith2, Anestis Tsakiridis1

  • 1Centre for Stem Cell Biology, Department of Biomedical Science, The University of Sheffield, Sheffield, United Kingdom.

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|June 8, 2021
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Summary

Human pluripotent stem cells (hPSCs) can be differentiated into enteric nervous system (ENS) progenitors and neurons. This protocol offers a promising avenue for studying and treating enteric neuropathies.

Keywords:
ENS progenitorshPSCshuman pluripotent stem cellsvagal neural crest

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Area of Science:

  • Developmental biology
  • Stem cell biology
  • Neuroscience

Background:

  • The enteric nervous system (ENS) regulates gastrointestinal function and homeostasis.
  • ENS development originates from vagal neural crest (NC) cells.
  • Defects in ENS development lead to untreatable enteric neuropathies.

Purpose of the Study:

  • To describe a differentiation strategy for generating enteric neural progenitors and neurons from human pluripotent stem cells (hPSCs).
  • To establish an in vitro model for studying human ENS development and pathology.
  • To explore potential cell therapy applications for enteric neuropathies.

Main Methods:

  • Utilizing a combination of instructive signals and retinoic acid for dose/time-dependent differentiation.
  • Guiding hPSCs through a vagal neural crest (NC) intermediate.
  • Culturing cells in neurotrophic media to promote enteric neuron and glia development.

Main Results:

  • Successfully derived enteric neural progenitors from hPSCs via a vagal NC intermediate.
  • Demonstrated the differentiation of these progenitors into functional enteric neurons and glia.
  • Established detailed protocols for hPSC-based ENS cell generation.

Conclusions:

  • hPSCs provide a viable in vitro source for enteric neurons.
  • This differentiation strategy facilitates research into ENS development and disease.
  • The protocol holds potential for future cell-based therapeutic strategies for enteric neuropathies.