ArticleNature2016
Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 6 of them syntheses that pooled it.
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Who cites it
173 citing papers in PubMed, 6 syntheses or guidelines pooled it, 299 citations in OpenAlex.
- Bibliometric analysis of clinical treatment in Hirschsprung disease: trends and emerging hotspots.Frontiers in pediatrics · 2026Pooled it
- Pooled it
- Management and outcomes for long-segment Hirschsprung disease: A systematic review from the APSA Outcomes and Evidence Based Practice Committee.Journal of pediatric surgery · 2021Pooled it
- Enterochromaffin Cells: Sentinels to Gut Microbiota in Hyperalgesia?Frontiers in cellular and infection microbiology · 2021Pooled it
- Optogenetic control of the enteric nervous system and gastrointestinal transit.Expert review of gastroenterology & hepatology · 2019Pooled it
- Trans-ethnic meta-analysis of genome-wide association studies for Hirschsprung disease.Human molecular genetics · 2016Pooled it
- Sacral Neural Crest-Derived Extracellular Vesicles Promote Pelvic Ganglion Repair Through Anti-Pyroptotic Effects Involving ANXA1-FPR2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Laminin β4 is required for the development of human peripheral sensory neurons.Development (Cambridge, England) · 2026Article
- Adrenomedullary Organoids Derived from Neural Crest and Schwann Cell Precursors.Research square · 2026Article
- Distinct differentiation trajectories leave lasting impacts on gene regulation and function of V2a neurons.Nature communications · 2026Article
- Functional maturation of enteric neurons derived from human induced pluripotent stem cells.Stem cell reports · 2026Article
- Intestinal muscularis in health and disease.Communications biology · 2026Review
- The Motor Neuromuscular Axis: The Overlooked Element of Developmental Programming in Diabetes and Metabolic Syndrome.International journal of molecular sciences · 2026Review
- TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation.Nature communications · 2026Article
- ENS lineage potential is not intrinsically regionalized but is modulated by PTPRZ1 signaling.bioRxiv : the preprint server for biology · 2026Article
- Unlocking the Neurogenic Potential of Enteric Glial Cells for Hirschsprung Disease Therapy.Cellular and molecular gastroenterology and hepatology · 2026Article
- Methods to Isolate Enteric Glia from hPSC-Derived Enteric Ganglioids.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Jawbone-like organoids generated from human pluripotent stem cells.Nature biomedical engineering · 2025Article
- A call for a unified and multimodal definition of cellular identity in the enteric nervous system.The EMBO journal · 2025Article
- Article
113 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
The enteric nervous system (ENS) is the largest component of the autonomic nervous system, with neuron numbers surpassing those present in the spinal cord. The ENS has been called the 'second brain' given its autonomy, remarkable neurotransmitter diversity and complex cytoarchitecture. Defects in ENS development are responsible for many human disorders including Hirschsprung disease (HSCR). HSCR is caused by the developmental failure of ENS progenitors to migrate into the gastrointestinal tract, particularly the distal colon. Human ENS development remains poorly understood owing to the lack of an easily accessible model system. Here we demonstrate the efficient derivation and isolation of ENS progenitors from human pluripotent stem (PS) cells, and their further differentiation into functional enteric neurons. ENS precursors derived in vitro are capable of targeted migration in the developing chick embryo and extensive colonization of the adult mouse colon. The in vivo engraftment and migration of human PS-cell-derived ENS precursors rescue disease-related mortality in HSCR mice (Ednrb(s-l/s-l)), although the mechanism of action remains unclear. Finally, EDNRB-null mutant ENS precursors enable modelling of HSCR-related migration defects, and the identification of pepstatin A as a candidate therapeutic target. Our study establishes the first, to our knowledge, human PS-cell-based platform for the study of human ENS development, and presents cell- and drug-based strategies for the treatment of HSCR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.