Chondroitin sulphate/dermatan sulphate proteoglycans: potential regulators of corneal stem/progenitor cell phenotype in vitro

Bains, Kiranjit K. ORCID: https://orcid.org/0000-0001-6617-5768, Ashworth, Sean, Koudouna, Elena ORCID: https://orcid.org/0000-0002-9959-4667, Young, Robert D. ORCID: https://orcid.org/0000-0002-8300-8002, Hughes, Clare E. ORCID: https://orcid.org/0000-0003-4726-5877 and Quantock, Andrew J. ORCID: https://orcid.org/0000-0002-2484-3120 2023. Chondroitin sulphate/dermatan sulphate proteoglycans: potential regulators of corneal stem/progenitor cell phenotype in vitro. International Journal of Molecular Sciences 24 (3) , 2095. 10.3390/ijms24032095

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Abstract

Chondroitin sulphate (CS) proteoglycans with variable sulphation-motifs along their glycosaminoglycan (GAG) chains are closely associated with the stem cell niche of articular cartilage, where they are believed to influence the characteristics of the resident stem cells. Here, we investigated the immunohistochemical distribution of hybrid CS/dermatan sulphate (DS) GAGs in the periphery of the adult chicken cornea, which is the location of the cornea’s stem cell niche in a number of species, using a monoclonal antibody, 6C3, that recognises a sulphation motif-specific CS/DS GAG epitope. This revealed positive labelling that was restricted to the subepithelial corneal stroma, as well as nearby bony structures within the sclera, called ossicles. When cultivated on cell culture dishes coated with 6C3-rich CS/DS, corneal stromal cells (keratocytes) that had been isolated from embryonic chicken corneas formed circular colonies, which took several days to reach confluency. A flow cytometric analysis of these keratocytes revealed changes in their expression levels of the indicative stem cell markers, Connexin 43 (Cx43), Paired Box 6 (PAX6), B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1), and C-X-C Chemokine Receptor 4 (CXCR4) suggestive of a less-differentiated phenotype compared with expression levels in cells not exposed to CS/DS. These findings support the view that CS/DS promotes the retention of a stem cell phenotype in corneal cells, much as it has been proposed to do in other connective tissues.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Optometry and Vision Sciences
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	MDPI
ISSN:	1661-6596
Date of First Compliant Deposit:	6 February 2023
Date of Acceptance:	16 January 2023
Last Modified:	10 Feb 2024 02:17
URI:	https://orca.cardiff.ac.uk/id/eprint/156509

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