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从人诱导多能干细胞中生成功能性结膜上皮,包括杯状细胞。

Generation of functional conjunctival epithelium, including goblet cells, from human iPSCs.

机构信息

Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

出版信息

Cell Rep. 2021 Feb 2;34(5):108715. doi: 10.1016/j.celrep.2021.108715.

DOI:10.1016/j.celrep.2021.108715
PMID:33535050
Abstract

The conjunctival epithelium, which covers the sclera (the white of the eye) and lines the inside of the eyelids, is essential for mucin secretion and the establishment of a healthy tear film. Here, we describe human conjunctival development in a self-formed ectodermal autonomous multi-zone (SEAM) of cells that were derived from human-induced pluripotent stem cells (hiPSCs) and mimic whole-eye development. Our data indicate that epidermal growth factor (EGF) drives the generation of cells with a conjunctival epithelial lineage. We also show that individual conjunctival cells can be sorted and reconstituted by cultivation into a functional conjunctival epithelium that includes mucin-producing goblet cells. Keratinocyte growth factor (KGF), moreover, is necessary for the maturation of hiPSC-derived conjunctival epithelium-particularly the goblet cells-indicating key complementary roles of EGF and KGF in directing the differentiation and maturation, respectively, of the human conjunctival epithelium.

摘要

结膜上皮覆盖巩膜(眼白)并衬于眼睑内面,对于粘蛋白分泌和建立健康的泪膜至关重要。在这里,我们描述了源自人诱导多能干细胞(hiPSC)并模拟全眼发育的自主形成外胚层多区(SEAM)细胞中的人结膜发育。我们的数据表明表皮生长因子(EGF)驱动具有结膜上皮谱系的细胞的产生。我们还表明,可以通过培养将单个结膜细胞分选并重建为包括分泌粘蛋白的杯状细胞的功能性结膜上皮。此外,角质细胞生长因子(KGF)对于 hiPSC 衍生的结膜上皮的成熟是必需的-特别是杯状细胞-表明 EGF 和 KGF 分别在指导人结膜上皮的分化和成熟方面具有关键的互补作用。

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