Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells
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 roden...
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Nature Portfolio
2017
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oai:doaj.org-article:98a0aa1a66ae46da8336099aaa7132152021-12-02T15:06:15ZColitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells10.1038/s41598-017-02890-y2045-2322https://doaj.org/article/98a0aa1a66ae46da8336099aaa7132152017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02890-yhttps://doaj.org/toc/2045-2322Abstract 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.Jaime Belkind-GersonHannah K. GrahamJustin ReynoldsRyo HottaNandor NagyLily ChengMichal KamionekHai Ning ShiCarol M. AherneAllan M. GoldsteinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) |
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Medicine R Science Q 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 Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells |
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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. |
format |
article |
author |
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 |
author_facet |
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 |
author_sort |
Jaime Belkind-Gerson |
title |
Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells |
title_short |
Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells |
title_full |
Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells |
title_fullStr |
Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells |
title_full_unstemmed |
Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells |
title_sort |
colitis promotes neuronal differentiation of sox2+ and plp1+ enteric cells |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/98a0aa1a66ae46da8336099aaa713215 |
work_keys_str_mv |
AT jaimebelkindgerson colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT hannahkgraham colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT justinreynolds colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT ryohotta colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT nandornagy colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT lilycheng colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT michalkamionek colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT hainingshi colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT carolmaherne colitispromotesneuronaldifferentiationofsox2andplp1entericcells AT allanmgoldstein colitispromotesneuronaldifferentiationofsox2andplp1entericcells |
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1718388530474909696 |