Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques

Epithelial cell injury and impaired epithelial regeneration are considered key features in HIV pathogenesis and contribute to HIV-induced generalized immune activation. Understanding the molecular mechanisms underlying the disrupted epithelial regeneration might provide an alternative approach for t...

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Autores principales:	Nongthombam Boby, Xuewei Cao, Alyssa Ransom, Barcley T. Pace, Christopher Mabee, Monica N. Shroyer, Arpita Das, Peter J. Didier, Sudesh K. Srivastav, Edith Porter, Qiuying Sha, Bapi Pahar
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	intestinal stem cell (ISC) SIV epithelial cells LGR5 alpha defensin Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/b5121de0ff944f71a8645d3377203f3d
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spelling	oai:doaj.org-article:b5121de0ff944f71a8645d3377203f3d2021-11-30T12:49:23ZIdentification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques1664-322410.3389/fimmu.2021.769990https://doaj.org/article/b5121de0ff944f71a8645d3377203f3d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.769990/fullhttps://doaj.org/toc/1664-3224Epithelial cell injury and impaired epithelial regeneration are considered key features in HIV pathogenesis and contribute to HIV-induced generalized immune activation. Understanding the molecular mechanisms underlying the disrupted epithelial regeneration might provide an alternative approach for the treatment of HIV-mediated enteropathy and immune activation. We have observed a significant increased presence of α defensin5+ (HD5) Paneth cells and proliferating Ki67+ epithelial cells as well as decreased expression of E-cadherin expression in epithelial cells during SIV infection. SIV infection did not significantly influence the frequency of LGR5+ stem cells, but the frequency of HD5+ cells was significantly higher compared to uninfected controls in jejunum. Our global transcriptomics analysis of enteroids provided novel information about highly significant changes in several important pathways like metabolic, TCA cycle, and oxidative phosphorylation, where the majority of the differentially expressed genes were downregulated in enteroids grown from chronically SIV-infected macaques compared to the SIV-uninfected controls. Despite the lack of significant reduction in LGR5+ stem cell population, the dysregulation of several intestinal stem cell niche factors including Notch, mTOR, AMPK and Wnt pathways as well as persistence of inflammatory cytokines and chemokines and loss of epithelial barrier function in enteroids further supports that SIV infection impacts on epithelial cell proliferation and intestinal homeostasis.Nongthombam BobyXuewei CaoAlyssa RansomBarcley T. PaceChristopher MabeeMonica N. ShroyerArpita DasPeter J. DidierSudesh K. SrivastavEdith PorterQiuying ShaBapi PaharBapi PaharBapi PaharFrontiers Media S.A.articleintestinal stem cell (ISC)SIVepithelial cellsLGR5alpha defensinImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intestinal stem cell (ISC) SIV epithelial cells LGR5 alpha defensin Immunologic diseases. Allergy RC581-607
spellingShingle	intestinal stem cell (ISC) SIV epithelial cells LGR5 alpha defensin Immunologic diseases. Allergy RC581-607 Nongthombam Boby Xuewei Cao Alyssa Ransom Barcley T. Pace Christopher Mabee Monica N. Shroyer Arpita Das Peter J. Didier Sudesh K. Srivastav Edith Porter Qiuying Sha Bapi Pahar Bapi Pahar Bapi Pahar Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques
description	Epithelial cell injury and impaired epithelial regeneration are considered key features in HIV pathogenesis and contribute to HIV-induced generalized immune activation. Understanding the molecular mechanisms underlying the disrupted epithelial regeneration might provide an alternative approach for the treatment of HIV-mediated enteropathy and immune activation. We have observed a significant increased presence of α defensin5+ (HD5) Paneth cells and proliferating Ki67+ epithelial cells as well as decreased expression of E-cadherin expression in epithelial cells during SIV infection. SIV infection did not significantly influence the frequency of LGR5+ stem cells, but the frequency of HD5+ cells was significantly higher compared to uninfected controls in jejunum. Our global transcriptomics analysis of enteroids provided novel information about highly significant changes in several important pathways like metabolic, TCA cycle, and oxidative phosphorylation, where the majority of the differentially expressed genes were downregulated in enteroids grown from chronically SIV-infected macaques compared to the SIV-uninfected controls. Despite the lack of significant reduction in LGR5+ stem cell population, the dysregulation of several intestinal stem cell niche factors including Notch, mTOR, AMPK and Wnt pathways as well as persistence of inflammatory cytokines and chemokines and loss of epithelial barrier function in enteroids further supports that SIV infection impacts on epithelial cell proliferation and intestinal homeostasis.
format	article
author	Nongthombam Boby Xuewei Cao Alyssa Ransom Barcley T. Pace Christopher Mabee Monica N. Shroyer Arpita Das Peter J. Didier Sudesh K. Srivastav Edith Porter Qiuying Sha Bapi Pahar Bapi Pahar Bapi Pahar
author_facet	Nongthombam Boby Xuewei Cao Alyssa Ransom Barcley T. Pace Christopher Mabee Monica N. Shroyer Arpita Das Peter J. Didier Sudesh K. Srivastav Edith Porter Qiuying Sha Bapi Pahar Bapi Pahar Bapi Pahar
author_sort	Nongthombam Boby
title	Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques
title_short	Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques
title_full	Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques
title_fullStr	Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques
title_full_unstemmed	Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques
title_sort	identification, characterization, and transcriptional reprogramming of epithelial stem cells and intestinal enteroids in simian immunodeficiency virus infected rhesus macaques
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b5121de0ff944f71a8645d3377203f3d
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Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques

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