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Updated: Dec 10, 2025
Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest
Thomas J R Frith1, Antigoni Gogolou1, James O S Hackland2
1University of Sheffield, Department of Biomedical Science, Sheffield, UK.
Insights
Researchers efficiently generated enteric nervous system (ENS) progenitors from human pluripotent stem cells (hPSCs). Retinoic acid is crucial for specifying these progenitors, which can form neurons and colonize the ENS, offering potential for cell therapy.
Area of Science:
- Developmental biology
- Stem cell biology
- Neuroscience
Background:
- The enteric nervous system (ENS) originates from vagal neural crest cells.
- ENS developmental defects lead to enteric neuropathies like Hirschsprung disease.
- Generating enteric neurons from human pluripotent stem cells (hPSCs) is crucial for disease modeling and regenerative medicine.
Purpose of the Study:
- To efficiently generate enteric nervous system (ENS) progenitors from hPSCs.
- To identify signals critical for early ENS progenitor specification.
- To assess the potential of hPSC-derived ENS progenitors for therapeutic applications.
Main Methods:
- Generation of ENS progenitors from hPSCs.
- Assessment of retinoic acid's role in vagal axial identity and ENS progenitor specification.
- In vitro differentiation into enteric neurons.
- In vivo transplantation studies in adult mice.
Main Results:
- Efficient and accelerated generation of ENS progenitors from hPSCs.
- Retinoic acid identified as critical for vagal axial identity and ENS progenitor specification.
- hPSC-derived ENS progenitors generated enteric neurons in vitro and successfully colonized the ENS in vivo.
Conclusions:
- hPSC-derived ENS progenitors can be efficiently generated and specified.
- Retinoic acid is a key signaling molecule for ENS progenitor development.
- hPSC-derived ENS progenitors hold promise for cell therapy in enteric neuropathies.
Abstract:
The enteric nervous system (ENS) is derived primarily from the vagal neural crest, a migratory multipotent cell population emerging from the dorsal neural tube between somites 1 and 7. Defects in the development and function of the ENS cause a range of enteric neuropathies, including Hirschsprung disease. Little is known about the signals that specify early ENS progenitors, limiting progress in the generation of enteric neurons from human pluripotent stem cells (hPSCs) to provide tools for disease modeling and regenerative medicine for enteric neuropathies. We describe the efficient and accelerated generation of ENS progenitors from hPSCs, revealing that retinoic acid is critical for the acquisition of vagal axial identity and early ENS progenitor specification. These ENS progenitors generate enteric neurons in vitro and, following in vivo transplantation, achieved long-term colonization of the ENS in adult mice. Thus, hPSC-derived ENS progenitors may provide the basis for cell therapy for defects in the ENS.
