A temporal single cell transcriptome atlas of zebrafish anterior segment development.
A temporal single cell transcriptome atlas of zebrafish anterior segment development.
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DOI：
10.1038/s41598-023-32212-4
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发表时间：
2023-04-06
影响因子：
4.6
通讯作者：
Famulski, J. K.
中科院分区：
文献类型：
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作者：
Vocking, Oliver;Famulski, J. K.
眼前节发育不全（ASD）会导致视力障碍，源于眼前节（AS）组织发育不良。 ASD 的发生与眼周间充质细胞 (POM) 的功能障碍有关。 POM 细胞分化为前段间充质 (ASM) 细胞，其定殖并产生 AS 组织。在这项研究中，我们揭示了与 AS 形成相关的 ASM 发育轨迹。使用在整个发育过程中荧光标记 ASM 的转基因斑马鱼系 Tg[foxc1b:GFP]，我们在几个发育时间点 (48–144 hpf) 分离了 GFP+ ASM 细胞，并进行了单细胞 RNA 测序。聚类分析表明 ASM 早在 48 hpf 时就已亚分化，随后分化为角膜上皮/内皮/基质或环形韧带 (AL) 谱系。跟踪各个簇揭示了 AL 和角膜内皮/基质的常见发育途径（直至 72 hpf）以及从 48 hpf 开始的角膜上皮的不同途径。对与 AS 发育相关的 80 多个基因进行的时空验证表明，哺乳动物小梁网和角膜组织具有高度保守性。此外，我们还描述了 13 个与环形韧带相关的新基因和 7 个与角膜发育相关的新基因。总体而言，这些数据为长期以来的假设提供了分子验证，即 POM 衍生的 ASM 产生 AS 组织，并强调了斑马鱼和哺乳动物之间的高度保守性。
Anterior segment dysgenesis (ASD), resulting in vision impairment, stems from maldevelopment of anterior segment (AS) tissues. Incidence of ASD has been linked to malfunction of periocular mesenchyme cells (POM). POM cells specify into anterior segment mesenchyme (ASM) cells which colonize and produce AS tissues. In this study we uncover ASM developmental trajectories associated with formation of the AS. Using a transgenic line of zebrafish that fluorescently labels the ASM throughout development, Tg[foxc1b:GFP], we isolated GFP+ ASM cells at several developmental timepoints (48–144 hpf) and performed single cell RNA sequencing. Clustering analysis indicates subdifferentiation of ASM as early as 48 hpf and subsequent diversification into corneal epithelium/endothelium/stroma, or annular ligament (AL) lineages. Tracking individual clusters reveals common developmental pathways, up to 72 hpf, for the AL and corneal endothelium/stroma and distinct pathways for corneal epithelium starting at 48 hpf. Spatiotemporal validation of over 80 genes found associated with AS development demonstrates a high degree of conservation with mammalian trabecular meshwork and corneal tissues. In addition, we characterize thirteen novel genes associated with annular ligament and seven with corneal development. Overall, the data provide a molecular verification of the long-standing hypothesis that POM derived ASM give rise to AS tissues and highlight the high degree of conservation between zebrafish and mammals.
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影响因子：
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作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
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作者：
Ha Thi BM;Campolmi N;He Z;Pipparelli A;Manissolle C;Thuret JY;Piselli S;Forest F;Peoc'h M;Garraud O;Gain P;Thuret G
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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