ArticleeLife2023
Age-associated changes in lineage composition of the enteric nervous system regulate gut health and disease.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 13 citations in OpenAlex.
- Gastrointestinal Disorders in Scleroderma.Gastroenterology · 2026Review
- Stress-induced glucocorticoid signaling impairs enteric neurotrophin BDNF-TrkB pathway and drives gastrointestinal dysmotility.The Journal of biological chemistry · 2026Article
- Dysregulation of GDNF and GFRα1 expression in multifactorial Hirschsprung disease.BMC research notes · 2026Article
- Self-localized ultrafast pencil beam for volumetric multiphoton imaging.Nature methods · 2026Article
- Inflammation rewires the enteric nervous system through neurogenic monocyte recruitment.The Journal of experimental medicine · 2026Article
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- Artery Tertiary Lymphoid Organs Form Neuroimmune Cardiovascular Interfaces in Atherosclerosis.Immunological reviews · 2026Review
- Reduced enteric BDNF-TrkB signaling drives stress-dependent glucocorticoid-mediated GI dysmotility.bioRxiv : the preprint server for biology · 2025Article
- Antimitochondrial antibodies in systemic sclerosis target enteric neurons and are associated with GI dysmotility.Annals of the rheumatic diseases · 2025Article
- The human colon: Evidence for degenerative changes during aging and the physiological consequences.Neurogastroenterology and motility · 2025Review
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- Article
- Nervous system-gut microbiota-immune system axis: future directions for preventing tumor.Frontiers in immunology · 2025Review
- Article
- Optimization of protocols for immunohistochemical assessment of enteric nervous system in formalin fixed human tissue.bioRxiv : the preprint server for biology · 2024Article
- Innervation of adipocytes is limited in mouse perivascular adipose tissue.American journal of physiology. Heart and circulatory physiology · 2024Article
- Smooth muscle contractile responses to bile acids in mouse ileum require TGR5 but not ASBT.Frontiers in neurology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
The enteric nervous system (ENS), a collection of neural cells contained in the wall of the gut, is of fundamental importance to gastrointestinal and systemic health. According to the prevailing paradigm, the ENS arises from progenitor cells migrating from the neural crest and remains largely unchanged thereafter. Here, we show that the lineage composition of maturing ENS changes with time, with a decline in the canonical lineage of neural-crest derived neurons and their replacement by a newly identified lineage of mesoderm-derived neurons. Single cell transcriptomics and immunochemical approaches establish a distinct expression profile of mesoderm-derived neurons. The dynamic balance between the proportions of neurons from these two different lineages in the post-natal gut is dependent on the availability of their respective trophic signals, GDNF-RET and HGF-MET. With increasing age, the mesoderm-derived neurons become the dominant form of neurons in the ENS, a change associated with significant functional effects on intestinal motility which can be reversed by GDNF supplementation. Transcriptomic analyses of human gut tissues show reduced GDNF-RET signaling in patients with intestinal dysmotility which is associated with reduction in neural crest-derived neuronal markers and concomitant increase in transcriptional patterns specific to mesoderm-derived neurons. Normal intestinal function in the adult gastrointestinal tract therefore appears to require an optimal balance between these two distinct lineages within the ENS.
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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.