PT  - JOURNAL ARTICLE
AU  - Thomas J.R Frith
AU  - Antigoni Gogolou
AU  - James O.S Hackland
AU  - Ivana Barbaric
AU  - Nikhil Thapar
AU  - Alan J. Burns
AU  - Peter W Andrews
AU  - Anestis Tsakiridis
AU  - Conor J. McCann
TI  - Retinoic acid accelerates the specification of enteric neural progenitors from <em>in vitro</em>-derived neural crest
AID  - 10.1101/819748
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 819748
4099  - http://biorxiv.org/content/early/2019/10/31/819748.short
4100  - http://biorxiv.org/content/early/2019/10/31/819748.full
AB  - 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 1-7. Defects in the development and function of the ENS give rise to a range of disorders, termed enteric neuropathies and include conditions such as Hirschsprung’s disease. Little is known about the signalling that specifies early ENS progenitors. This has, thus far, limited progress in the generation of enteric neurons from human Pluripotent Stem Cells (hPSCs) that could provide a useful tool for disease modelling and regenerative medicine. We describe the efficient and accelerated generation of ENS progenitors from hPSCs, revealing that retinoic acid is critical for the acquisition of both vagal axial identity and early ENS progenitor specification. These ENS progenitors generate enteric neurons in vitro and following in vivo transplantation, achieving long-term colonisation of the ENS in adult mice. Thus, hPSC-derived ENS progenitors may provide the basis for cell therapy for defects in the ENS.