Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest

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.