Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation

Detalhes bibliográficos
Autor(a) principal: Gesteira, Tarsis F. [UNIFESP]
Data de Publicação: 2017
Outros Autores: Sun, Mingxia, Coulson-Thomas, Yvette M. [UNIFESP], Yamaguchi, Yu, Yeh, Lung-Kun, Hascall, Vincent, Coulson-Thomas, Vivien J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://repositorio.unifesp.br/handle/11600/51303
http://dx.doi.org/10.1167/iovs.17-22326
Resumo: PURPOSE. Limbal epithelial stem cells (LSCs), located in the basal layer of the corneal epithelium in the corneal limbus, are vital for maintaining the corneal epithelium. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. To date, limited research has focused on unveiling the composition of the limbal stem cell niche, and, more important, on the role the specific stem cell niche may have in LSC differentiation and function. Our work investigates the composition of the extracellular matrix in the LSC niche and how it regulates LSC differentiation and function. METHODS. Hyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice-HAS1(-/-)
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spelling Gesteira, Tarsis F. [UNIFESP]Sun, MingxiaCoulson-Thomas, Yvette M. [UNIFESP]Yamaguchi, YuYeh, Lung-KunHascall, VincentCoulson-Thomas, Vivien J.2019-08-19T11:48:38Z2019-08-19T11:48:38Z2017Investigative Ophthalmology & Visual Science. Rockville, v. 58, n. 11, p. 4407-4421, 2017.0146-0404http://repositorio.unifesp.br/handle/11600/51303http://dx.doi.org/10.1167/iovs.17-22326WOS000410944300001.pdf10.1167/iovs.17-22326WOS:000410944300001PURPOSE. Limbal epithelial stem cells (LSCs), located in the basal layer of the corneal epithelium in the corneal limbus, are vital for maintaining the corneal epithelium. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. To date, limited research has focused on unveiling the composition of the limbal stem cell niche, and, more important, on the role the specific stem cell niche may have in LSC differentiation and function. Our work investigates the composition of the extracellular matrix in the LSC niche and how it regulates LSC differentiation and function. METHODS. Hyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice-HAS1(-/-)HAS3(-/-), HAS2(Delta/Delta CorEpi), TSG-6(-/-) -were used to determine the importance of the HA niche in LSC differentiation and specification. RESULTS. Our data demonstrate that the LSC niche is composed of a HA rich extracellular matrix. HAS1(-/-)HAS3(-/-), HAS2(Delta/Delta CorEpi), and TSG-6(-/-) mice have delayed wound healing and increased inflammation after injury. Interestingly, upon insult the HAS knock-out mice upregulate HA throughout the cornea through a compensatory mechanism, and in turn this alters LSC and epithelial cell specification. CONCLUSIONS. The LSC niche is composed of a specialized HA matrix that differs from that present in the rest of the corneal epithelium, and the disruption of this specific HA matrix within the LSC niche leads to compromised corneal epithelial regeneration. Finally, our findings suggest that HA has a major role in maintaining the LSC phenotype.University of HoustonMizutani FoundationNational Institutes of Health (NIH)/National Eye InstituteUniv Fed São Paulo, São Paulo, BrazilUniv Houston, Coll Optometry, 4901 Calhoun Rd, Houston, TX 77204 USASanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA USAChang Gung Univ, Chang Gung Mem Hosp, Dept Ophthalmol, Coll Med, Linkou, TaiwanCleveland Clin, Cleveland, OH 44106 USAUniv Fed São Paulo, São Paulo, BrazilNIH: P30 EY07551Web of Science4407-4421engAssoc Research Vision Ophthalmology Inclimbal stem cellshyaluronancorneal epithelial cellsstem cell nicheHyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000410944300001.pdfapplication/pdf2468269${dspace.ui.url}/bitstream/11600/51303/1/WOS000410944300001.pdfaecba1232506e66b7238b02589b48525MD51open accessTEXTWOS000410944300001.pdf.txtWOS000410944300001.pdf.txtExtracted texttext/plain78208${dspace.ui.url}/bitstream/11600/51303/2/WOS000410944300001.pdf.txt0532da18c02631717889a30304805f2dMD52open accessTHUMBNAILWOS000410944300001.pdf.jpgWOS000410944300001.pdf.jpgIM Thumbnailimage/jpeg7743${dspace.ui.url}/bitstream/11600/51303/4/WOS000410944300001.pdf.jpg59fc257aec93cc76a1057838192245e9MD54open access11600/513032022-08-01 18:39:39.439open accessoai:repositorio.unifesp.br:11600/51303Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:17:10.713526Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.en.fl_str_mv Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
title Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
spellingShingle Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
Gesteira, Tarsis F. [UNIFESP]
limbal stem cells
hyaluronan
corneal epithelial cells
stem cell niche
title_short Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
title_full Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
title_fullStr Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
title_full_unstemmed Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
title_sort Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
author Gesteira, Tarsis F. [UNIFESP]
author_facet Gesteira, Tarsis F. [UNIFESP]
Sun, Mingxia
Coulson-Thomas, Yvette M. [UNIFESP]
Yamaguchi, Yu
Yeh, Lung-Kun
Hascall, Vincent
Coulson-Thomas, Vivien J.
author_role author
author2 Sun, Mingxia
Coulson-Thomas, Yvette M. [UNIFESP]
Yamaguchi, Yu
Yeh, Lung-Kun
Hascall, Vincent
Coulson-Thomas, Vivien J.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Gesteira, Tarsis F. [UNIFESP]
Sun, Mingxia
Coulson-Thomas, Yvette M. [UNIFESP]
Yamaguchi, Yu
Yeh, Lung-Kun
Hascall, Vincent
Coulson-Thomas, Vivien J.
dc.subject.eng.fl_str_mv limbal stem cells
hyaluronan
corneal epithelial cells
stem cell niche
topic limbal stem cells
hyaluronan
corneal epithelial cells
stem cell niche
description PURPOSE. Limbal epithelial stem cells (LSCs), located in the basal layer of the corneal epithelium in the corneal limbus, are vital for maintaining the corneal epithelium. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. To date, limited research has focused on unveiling the composition of the limbal stem cell niche, and, more important, on the role the specific stem cell niche may have in LSC differentiation and function. Our work investigates the composition of the extracellular matrix in the LSC niche and how it regulates LSC differentiation and function. METHODS. Hyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice-HAS1(-/-)
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2019-08-19T11:48:38Z
dc.date.available.fl_str_mv 2019-08-19T11:48:38Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv Investigative Ophthalmology & Visual Science. Rockville, v. 58, n. 11, p. 4407-4421, 2017.
dc.identifier.uri.fl_str_mv http://repositorio.unifesp.br/handle/11600/51303
http://dx.doi.org/10.1167/iovs.17-22326
dc.identifier.issn.none.fl_str_mv 0146-0404
dc.identifier.file.none.fl_str_mv WOS000410944300001.pdf
dc.identifier.doi.none.fl_str_mv 10.1167/iovs.17-22326
dc.identifier.wos.none.fl_str_mv WOS:000410944300001
identifier_str_mv Investigative Ophthalmology & Visual Science. Rockville, v. 58, n. 11, p. 4407-4421, 2017.
0146-0404
WOS000410944300001.pdf
10.1167/iovs.17-22326
WOS:000410944300001
url http://repositorio.unifesp.br/handle/11600/51303
http://dx.doi.org/10.1167/iovs.17-22326
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv 4407-4421
dc.publisher.none.fl_str_mv Assoc Research Vision Ophthalmology Inc
publisher.none.fl_str_mv Assoc Research Vision Ophthalmology Inc
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
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collection Repositório Institucional da UNIFESP
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