Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
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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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 |
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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 |
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Assoc Research Vision Ophthalmology Inc |
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Assoc Research Vision Ophthalmology Inc |
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