In 2021, transcriptome analysis of the mouse and human gut advanced our understanding of the cellular composition, development and surrounding non-neural context of the enteric nervous system (ENS). A role for the ENS in tuning regulatory T cell proportions contributed insights into the dependency between the ENS, immune system and microbiota.
Key advances
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Single-cell transcriptome analysis and histochemistry revealed 12 myenteric neuron classes in the mouse small intestine and a conceptually new step-wise principle for their embryonic diversification5.
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A monumental single-cell transcriptome atlas of the human gut across time and space described the development of the enteric nervous system (ENS) and the non-neural cellular context of the fetal, paediatric and adult ENS7.
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Enteric neurons tune the number and phenotypes of regulatory T cells by secretion of IL-6; in turn, the structure and activity of the ENS is modulated by microbial signals, altogether suggesting tripartite interactions between the ENS, immune system and microbiota, of relevance for intestinal tolerance10.
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References
Wang, H., Foong, J. P. P., Harris, N. L. & Bornstein, J. C. Enteric neuroimmune interactions coordinate intestinal responses in health and disease. Mucosal Immunol. https://doi.org/10.1038/s41385-021-00443-1 (2021).
Zeisel, A. et al. Molecular architecture of the mouse nervous system. Cell 174, 999–1014 (2018).
Drokhlyansky, E. et al. The human and mouse enteric nervous system at single-cell resolution. Cell 182, 1606–1622 (2020).
May-Zhang, A. A. et al. Combinatorial transcriptional profiling of mouse and human enteric neurons identifies shared and disparate subtypes in situ. Gastroenterology 160, 755–770 (2021).
Morarach, K. et al. Diversification of molecularly defined myenteric neuron classes revealed by single-cell RNA sequencing. Nat. Neurosci. 24, 34–46 (2021).
Wright, C. M. et al. scRNA-seq reveals new enteric nervous system roles for GDNF, NRTN and TBX3. Cell Mol. Gastroenterol. Hepatol. 11, 1548–1592 (2021).
Elmentaite, R. et al. Cells of the human intestinal tract mapped across space and time. Nature 597, 250–255 (2021).
Holloway, E. M. et al. Mapping development of the human intestinal niche at single-cell resolution. Cell Stem Cell 28, 568–580 (2021).
Fawkner-Corbett, D. et al. Spatiotemporal analysis of human intestinal development at single-cell resolution. Cell 184, 810–826 (2021).
Yan, Y. et al. Interleukin-6 produced by enteric neurons regulates the number and phenotype of microbe-responsive regulatory T cells in the gut. Immunity 54, 499–513 (2021).
Acknowledgements
The laboratory of U.M. is supported by the Swedish Research Council (2020-01129), Knut & Alice Wallenberg Foundation (2020.0109), NIH, Brain Foundation, Ollie and Elof Ericsson’s Foundation, and SFO Stem Cells and Regeneration.
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Marklund, U. Diversity, development and immunoregulation of enteric neurons. Nat Rev Gastroenterol Hepatol 19, 85–86 (2022). https://doi.org/10.1038/s41575-021-00553-y
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DOI: https://doi.org/10.1038/s41575-021-00553-y
