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://dx.doi.org/10.1167/iovs.17-22326
http://repositorio.unifesp.br/handle/11600/51303
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 Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiationlimbal stem cellshyaluronancorneal epithelial cellsstem cell nichePURPOSE. 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.Univ 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, BrazilWeb of ScienceUniversity of HoustonMizutani FoundationNational Institutes of Health (NIH)/National Eye InstituteNIH: P30 EY07551Assoc Research Vision Ophthalmology Inc2019-08-19T11:48:38Z2019-08-19T11:48:38Z2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion4407-4421application/pdfhttp://dx.doi.org/10.1167/iovs.17-22326Investigative Ophthalmology & Visual Science. Rockville, v. 58, n. 11, p. 4407-4421, 2017.10.1167/iovs.17-22326WOS000410944300001.pdf0146-0404http://repositorio.unifesp.br/handle/11600/51303WOS:000410944300001enginfo:eu-repo/semantics/openAccessGesteira, Tarsis F. [UNIFESP]Sun, MingxiaCoulson-Thomas, Yvette M. [UNIFESP]Yamaguchi, YuYeh, Lung-KunHascall, VincentCoulson-Thomas, Vivien J.reponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-10T21:40:44Zoai:repositorio.unifesp.br/:11600/51303Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-10T21:40:44Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.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.por.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.none.fl_str_mv 2017
2019-08-19T11:48:38Z
2019-08-19T11:48:38Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1167/iovs.17-22326
Investigative Ophthalmology & Visual Science. Rockville, v. 58, n. 11, p. 4407-4421, 2017.
10.1167/iovs.17-22326
WOS000410944300001.pdf
0146-0404
http://repositorio.unifesp.br/handle/11600/51303
WOS:000410944300001
url http://dx.doi.org/10.1167/iovs.17-22326
http://repositorio.unifesp.br/handle/11600/51303
identifier_str_mv Investigative Ophthalmology & Visual Science. Rockville, v. 58, n. 11, p. 4407-4421, 2017.
10.1167/iovs.17-22326
WOS000410944300001.pdf
0146-0404
WOS:000410944300001
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 4407-4421
application/pdf
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)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
_version_ 1814268290254503936

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