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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2020 Aug 29

PMID 32857978

Citations 14

Authors

Thomas J R Frith

Antigoni Gogolou

James O S Hackland

Zoe A Hewitt

Harry D Moore

Ivana Barbaric

Nikhil Thapar

Alan J Burns

Peter W Andrews

Anestis Tsakiridis

Conor J McCann

Affiliations

Soon will be listed here.

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.

Citing Articles

Rdh10-mediated Retinoic Acid Signaling Regulates the Neural Crest Cell Microenvironment During ENS Formation.

Tjaden N, Shannon S, Seidel C, Childers M, Aoto K, Sandell L bioRxiv. 2025; .

PMID: 39896510 PMC: 11785139. DOI: 10.1101/2025.01.23.634504.

Human enteric nervous system progenitor transplantation improves functional responses in Hirschsprung disease patient-derived tissue.

Jevans B, Cooper F, Fatieieva Y, Gogolou A, Kang Y, Restuadi R Gut. 2024; 73(9):1441-1453.

PMID: 38816188 PMC: 11347211. DOI: 10.1136/gutjnl-2023-331532.

Induction and staging of human gastruloids with neural tube, segmented somites & advanced cell types.

Hamazaki N, Yang W, Kubo C, Qiu C, Martin B, Garge R bioRxiv. 2024; .

PMID: 38405970 PMC: 10888963. DOI: 10.1101/2024.02.10.579769.

Updates and Challenges in ENS Cell Therapy for the Treatment of Neurointestinal Diseases.

Ohkura T, Burns A, Hotta R Biomolecules. 2024; 14(2).

PMID: 38397466 PMC: 10887039. DOI: 10.3390/biom14020229.

In Vivo Tumorigenicity of the 20q11.21 Amplicon in an Engraftment Model of hPSCs and Differentiated Liver Cells.

Pridgeon C, Forootan S, Zhang F, Harper N, Palmer D, Weightmann R J Stem Cells Regen Med. 2023; 19(1):3-13.

PMID: 37366409 PMC: 10290816. DOI: 10.46582/jsrm.1901002.

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