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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Autores principales: 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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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/98a0aa1a66ae46da8336099aaa713215
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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
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