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Transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation

BACKGROUND: Development of primary open-angle glaucoma (POAG) is associated with the malfunctioning trabecular meshwork (TM). Cell therapy offers great potential for the treatment of POAG, but requires the generation of functional TM cells in vitro to replace the lost/dysfunctional cells. TM differe...

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Autores principales: Sathiyanathan, Padmapriya, Tay, Cheryl Y., Stanton, Lawrence W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436446/
https://www.ncbi.nlm.nih.gov/pubmed/28514956
http://dx.doi.org/10.1186/s12864-017-3758-7
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author Sathiyanathan, Padmapriya
Tay, Cheryl Y.
Stanton, Lawrence W.
author_facet Sathiyanathan, Padmapriya
Tay, Cheryl Y.
Stanton, Lawrence W.
author_sort Sathiyanathan, Padmapriya
collection PubMed
description BACKGROUND: Development of primary open-angle glaucoma (POAG) is associated with the malfunctioning trabecular meshwork (TM). Cell therapy offers great potential for the treatment of POAG, but requires the generation of functional TM cells in vitro to replace the lost/dysfunctional cells. TM differentiation in vitro from various stem cell types must be monitored by the expression of specific markers. However, no single definitive marker of the TM has been identified. RESULTS: To identify robust markers of TM differentiation, we performed global transcriptome profiling using high-density oligonucleotide microarray on ex vivo TM tissue and cultured TM progenitors. Corneal and scleral tissues were also used in the analysis. After removal of genes expressed in the cornea and sclera, 18 genes were identified that were differentially expressed in the TM relative to the other samples. CDH23, F5, KCNAB1, FGF9, SPP1, and HEY1 were selected among the genes highly expressed in the TM, together with BDNF which was repressed, compared to progenitors for further investigation. Expression analysis by qPCR verified the differential expression and immunofluorescence of the anterior segment confirmed strong expression in the TM. CONCLUSIONS: Three independent cohort of expression studies have identified novel markers, fitting in identifying TM cells and in evaluating directed TM differentiation in vitro. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3758-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-54364462017-05-19 Transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation Sathiyanathan, Padmapriya Tay, Cheryl Y. Stanton, Lawrence W. BMC Genomics Research Article BACKGROUND: Development of primary open-angle glaucoma (POAG) is associated with the malfunctioning trabecular meshwork (TM). Cell therapy offers great potential for the treatment of POAG, but requires the generation of functional TM cells in vitro to replace the lost/dysfunctional cells. TM differentiation in vitro from various stem cell types must be monitored by the expression of specific markers. However, no single definitive marker of the TM has been identified. RESULTS: To identify robust markers of TM differentiation, we performed global transcriptome profiling using high-density oligonucleotide microarray on ex vivo TM tissue and cultured TM progenitors. Corneal and scleral tissues were also used in the analysis. After removal of genes expressed in the cornea and sclera, 18 genes were identified that were differentially expressed in the TM relative to the other samples. CDH23, F5, KCNAB1, FGF9, SPP1, and HEY1 were selected among the genes highly expressed in the TM, together with BDNF which was repressed, compared to progenitors for further investigation. Expression analysis by qPCR verified the differential expression and immunofluorescence of the anterior segment confirmed strong expression in the TM. CONCLUSIONS: Three independent cohort of expression studies have identified novel markers, fitting in identifying TM cells and in evaluating directed TM differentiation in vitro. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3758-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-17 /pmc/articles/PMC5436446/ /pubmed/28514956 http://dx.doi.org/10.1186/s12864-017-3758-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sathiyanathan, Padmapriya
Tay, Cheryl Y.
Stanton, Lawrence W.
Transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation
title Transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation
title_full Transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation
title_fullStr Transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation
title_full_unstemmed Transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation
title_short Transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation
title_sort transcriptome analysis for the identification of cellular markers related to trabecular meshwork differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436446/
https://www.ncbi.nlm.nih.gov/pubmed/28514956
http://dx.doi.org/10.1186/s12864-017-3758-7
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