The enteric nervous system (ENS) coordinates diverse functions in the intestine but has eluded comprehensive molecular characterization because of the rarity and diversity of cells. Here we develop two methods to profile the ENS of adult mice and humans at single-cell resolution: RAISIN RNA-seq for profiling intact nuclei with ribosome-bound mRNA and MIRACL-seq for label-free enrichment of rare cell types by droplet-based profiling. The 1,187,535 nuclei in our mouse atlas include 5,068 neurons from the ileum and colon, revealing extraordinary neuron diversity. We highlight circadian expression changes in enteric neurons, show that disease-related genes are dysregulated with aging, and identify differences between the ileum and proximal/distal colon. In humans, we profile 436,202 nuclei, recovering 1,445 neurons, and identify conserved and species-specific transcriptional programs and putative neuro-epithelial, neuro-stromal, and neuro-immune interactions. The human ENS expresses risk genes for neuropathic, inflammatory, and extra-intestinal diseases, suggesting neuronal contributions to disease.
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http://dx.doi.org/10.1016/j.cell.2020.08.003 | DOI Listing |
Gastroenterology
December 2024
Department of Clinical Genetics, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Pediatric Surgery, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands. Electronic address:
Background And Aims: The enteric nervous system (ENS), comprised of neurons and glia, regulates intestinal motility. Hirschsprung disease (HSCR) results from defects in ENS formation, yet while neuronal aspects have been extensively studied, enteric glia remain disregarded. This study aimed to explore enteric glia diversity in health and disease.
View Article and Find Full Text PDFCancer Lett
December 2024
Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China. Electronic address:
A malignant tumor is a complex systemic disease involving the nervous system, which regulates nerve signals. Cancer neuroscience is a field that explores the interactions between tumors and the nervous system. The gastrointestinal tract is a typical peripheral organ with abundant neuroregulation and is regulated by the peripheral, enteric, and central nervous systems (PNS, ENS, and CNS, respectively).
View Article and Find Full Text PDFBrain
December 2024
School of Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK.
Convergent data, across species, paint a compelling picture of the critical role of the gut and its resident microbiota in several brain functions and disorders. The chemicals mediating communication along these sophisticated highways of the brain-gut-microbiome (BGM) axis include both microbiota metabolites and classical neurotransmitters. Amongst the latter, GABA is fundamental to brain function where it mediates the majority of neuronal inhibition.
View Article and Find Full Text PDFMucosal Immunol
December 2024
Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK. Electronic address:
Neuro-immune interactions within barrier organs, such as lung, gut, and skin, are crucial in regulating tissue homeostasis, inflammatory responses, and host defence. Our rapidly advancing understanding of peripheral neuroimmunology is transforming the field of barrier tissue immunology, offering a fresh perspective for developing therapies for complex chronic inflammatory disorders affecting barrier organs. However, most studies have primarily examined interactions between the peripheral nervous system and the immune system from a neuron-focused perspective, while glial cells, the nonneuronal cells of the nervous system, have received less attention.
View Article and Find Full Text PDFBMC Womens Health
December 2024
Department of Basic Sciences - Physiology Division, Ponce Health Sciences University, Ponce Research Institute, PO Box 7004, Ponce, 00732-7004, PR, Puerto Rico.
Background: Endometriosis is a complex gynecological disorder characterized by the ectopic growth of endometrial tissue. Symptoms of endometriosis are known to impair the quality of life of patients, and among these are found dysmenorrhea, chronic pelvic pain, and gastrointestinal (GI) issues. GI issues such as painful bowel movements, bloating and constipation or diarrhea, are one of the common reasons for misdiagnosis with irritable bowel syndrome (IBS).
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