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| Item Type: | Article |
|---|---|
| Title: | A transcriptional atlas of gut-innervating neurons reveals activation of interferon signaling and ferroptosis during intestinal inflammation |
| Creators Name: | Forster, P.M., Jakob, M.O., Yusuf, D., Bubeck, M., Limberger, H., Luo, Y., Thieme, P., Polici, A., Sterczyk, N., Boulekou, S., Bartel, L., Cosovanu, C., Witkowski, M., González-Acera, M., Kühl, A.A., Weidinger, C., Backofen, R., Hegazy, A.N., Patankar, J.V. and Klose, C.S.N. |
| Abstract: | Enteric infections often cause long-term sequelae, including persistent gastrointestinal symptoms, such as pain, discomfort, or irritable bowel syndrome. The plethora of sensory symptoms indicates that gut-innervating neurons might be directly affected by inflammation. However, sequencing studies of neurons in the gastrointestinal tract are hampered by difficulties in purifying neurons, especially during inflammation. Activating a nuclear GFP tag selectively in neurons enabled sort purification of intrinsic and extrinsic neurons of the gastrointestinal tract in models of intestinal inflammation. Using bulk and single-nucleus RNA sequencing, we mapped the whole transcriptomic landscape and identified a conserved neuronal response to inflammation, which included the interferon signaling and ferroptosis pathway. Deletion of the interferon receptor 1 in neurons regulated ferroptosis, neuronal loss, and consequently gut-transit time. Collectively, this study offers a resource documenting neuronal adaptation to inflammatory conditions and exposes the interferon and ferroptosis pathways as signaling cascades activated in neurons during inflammation. |
| Keywords: | Neuro-Immune Interactions, Enteric Nervous System, Extrinsic Innervation of the Intestine, Intestinal Inflammation, Ferroptosis, Interferons, Lipid Peroxidation, Intestinal Motility, Inflammatory Bowel Disease, Animals, Mice |
| Source: | Neuron |
| ISSN: | 0896-6273 |
| Publisher: | Cell Press |
| Date: | 17 March 2025 |
| Additional Information: | Leif S.-H. Ludwig and Ashley Sanders are members of TRR241 IBDome Consortium. |
| Official Publication: | https://doi.org/10.1016/j.neuron.2025.02.018 |
| PubMed: | View item in PubMed |
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