Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells

Jaime Belkind-Gerson, Hannah K. Graham, Justin Reynolds, Ryo Hotta, Nandor Nagy, Lily Cheng, Michal Kamionek, Hai Ning Shi, Carol M. Aherne, Allan M. Goldstein

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Abstract

Mechanisms mediating adult enteric neurogenesis are largely unknown. Using inflammation-associated neurogenesis models and a transgenic approach, we aimed to understand the cell-source for new neurons in infectious and inflammatory colitis. Dextran sodium sulfate (DSS) and Citrobacter rodentium colitis (CC) was induced in adult mice and colonic neurons were quantified. Sox2GFP and PLP1GFP mice confirmed the cell-type specificity of these markers. Sox2CreER:YFP and PLP1creER:tdT mice were used to determine the fate of these cells after colitis. Sox2 expression was investigated in colonic neurons of human patients with Clostridium difficile or ulcerative colitis. Both DSS and CC led to increased colonic neurons. Following colitis in adult Sox2CreER:YFP mice, YFP initially expressed predominantly by glia becomes expressed by neurons following colitis, without observable DNA replication. Similarly in PLP1CreER:tdT mice, PLP1 cells that co-express S100b but not RET also give rise to neurons following colitis. In human colitis, Sox2-expressing neurons increase from 1-2% to an average 14% in colitis. The new neurons predominantly express calretinin, thus appear to be excitatory. These results suggest that colitis promotes rapid enteric neurogenesis in adult mice and humans through differentiation of Sox2-and PLP1-expressing cells, which represent enteric glia and/or neural progenitors. Further defining neurogenesis will improve understanding and treatment of injury-associated intestinal motility/sensory disorders.

Original languageEnglish
Article number2525
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Belkind-Gerson, J., Graham, H. K., Reynolds, J., Hotta, R., Nagy, N., Cheng, L., Kamionek, M., Shi, H. N., Aherne, C. M., & Goldstein, A. M. (2017). Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells. Scientific reports, 7(1), [2525]. https://doi.org/10.1038/s41598-017-02890-y