98%
921
2 minutes
20
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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486303 | PMC |
http://dx.doi.org/10.1016/j.stemcr.2020.07.024 | DOI Listing |
FASEB J
September 2025
Department of Biosciences, Rice University, Houston, Texas, USA.
The enteric nervous system (ENS) is the intrinsic nervous system of the gut and controls essential functions, such as gut motility, intestinal barrier function, and water balance. The ENS displays a complex 3D architecture within the context of the gut and specific transcriptional states needed to control gut homeostasis. During development, the ENS develops from enteric neural progenitor cells (ENPs) that migrate into the gut and differentiate into functionally diverse neuron types.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2025
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
The vertebrate enteric nervous system (ENS) is derived from vagal neural crest cells, which enter the foregut as progenitors that migrate from rostral to caudal to populate the entire length of the gut. Here, we show that transcription factors and , zebrafish orthologs of the human gene, are highly expressed in neural crest cells transitioning from progenitors to differentiating neuronal subtypes. Accordingly, CRISPR-Cas9 depletion shows that loss of paralogs reduces the number of neurons that express the inhibitory motor neuron marker without affecting cell proliferation or death.
View Article and Find Full Text PDFbioRxiv
July 2025
Department of Biology, University of Kentucky, Lexington, Kentucky 40506.
Neural crest cells (NCC) are vertebrate-specific multipotent progenitor cells that arise from the neural plate border and go on to contribute to a wide variety of morphological structures such as the jaw and palate, enteric nervous system (ENS), and pigment cells. Defects in essential steps in neural crest cell development have been associated with a wide variety of congenital disorders, collectively referred to as neurocristopathies. Her9/Hes4 is a bHLH-O transcriptional repressor that has been shown to regulate neural crest cell and craniofacial development in Xenopus and zebrafish, however the extent of Her9 function in other neural crest cell lineages has not been investigated.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
July 2025
Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Program in Human Genetics, Vanderbilt University, Nashville, Tennessee; Division of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: michelle.southard
Background & Aims: Enteric nervous system (ENS) development requires migration, proliferation, and differentiation of progenitors for normal gastrointestinal (GI) motility. Sox10 deficit causes aganglionosis, modeling Hirschsprung disease (HSCR), and disrupts ratios of postnatal enteric neurons in proximal ganglionated bowel. How Sox10 deficiency alters enteric neuron ratios is unclear.
View Article and Find Full Text PDFbioRxiv
July 2025
Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
The enteric nervous system (ENS) is a complex network of neurons and glial cells. Hirschsprung's disease (HSCR) is a congenital condition characterized by the absence of ganglion cells in the distal colon, leading to functional bowel obstruction. In this study, we used single-cell RNA sequencing (scRNA-seq) and whole genome sequencing (WGS) to analyze healthy and aganglionic colon segments from HSCR patients.
View Article and Find Full Text PDF