Chondroitin Sulfate as a Potential Modulator of the Stem Cell Niche in Cornea.
Chondroitin Sulfate as a Potential Modulator of the Stem Cell Niche in Cornea.
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DOI：
10.3389/fcell.2020.567358
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发表时间：
2020
影响因子：
5.5
通讯作者：
Quantock AJ
中科院分区：
文献类型：
--
作者：
Ashworth S;Harrington J;Hammond GM;Bains KK;Koudouna E;Hayes AJ;Ralphs JR;Regini JW;Young RD;Hayashi R;Nishida K;Hughes CE;Quantock AJ
硫酸软骨素（CS）是多种生物组织细胞外基质的重要组成部分。在角膜中，CS 糖胺聚糖 (GAG) 以杂合形式存在，其中一些重复二糖是硫酸皮肤素 (DS)。角膜中的这些 CS/DS GAG 通过存在于蛋白聚糖、核心蛋白聚糖和双糖链蛋白聚糖上，有助于控制胶原纤维的生成和组织。 CS 还充当一系列信号分子的调节配体，包括角膜生长和发育过程中的形态发生素、细胞因子、趋化因子和酶。越来越多的证据表明，具有特定硫酸化基序的 CS 或 CS/DS 的精确表达有助于定义有助于维持干细胞表型的局部细胞外区室。事实上，最近的证据表明，抗体 4C3、7D4 和 3B3 识别的 CS 硫酸化基序可识别干细胞群及其生态位，以及胎儿肘部组织发育的活化祖细胞和过渡区域。一些CS抗体识别的各种硫酸化基序也特异性地位于成熟角膜边缘的角膜缘区域，该区域被广泛认为代表角膜上皮干细胞生态位。新出现的数据还表明角膜形态发生过程中 CS 分布的发育变化。本文将反思 CS 和 CS/DS 在维持角膜干细胞生态位中的潜在作用，并将探讨 CS 可能参与人类 iPS（诱导多能干细胞）生成眼样组织的过程。
Chondroitin sulfate (CS) is an important component of the extracellular matrix in multiple biological tissues. In cornea, the CS glycosaminoglycan (GAG) exists in hybrid form, whereby some of the repeating disaccharides are dermatan sulfate (DS). These CS/DS GAGs in cornea, through their presence on the proteoglycans, decorin and biglycan, help control collagen fibrillogenesis and organization. CS also acts as a regulatory ligand for a spectrum of signaling molecules, including morphogens, cytokines, chemokines, and enzymes during corneal growth and development. There is a growing body of evidence that precise expression of CS or CS/DS with specific sulfation motifs helps define the local extracellular compartment that contributes to maintenance of the stem cell phenotype. Indeed, recent evidence shows that CS sulfation motifs recognized by antibodies 4C3, 7D4, and 3B3 identify stem cell populations and their niches, along with activated progenitor cells and transitional areas of tissue development in the fetal human elbow. Various sulfation motifs identified by some CS antibodies are also specifically located in the limbal region at the edge of the mature cornea, which is widely accepted to represent the corneal epithelial stem cell niche. Emerging data also implicate developmental changes in the distribution of CS during corneal morphogenesis. This article will reflect upon the potential roles of CS and CS/DS in maintenance of the stem cell niche in cornea, and will contemplate the possible involvement of CS in the generation of eye-like tissues from human iPS (induced pluripotent stem) cells.