Department of Genome Sciences, University of Washington, Seattle, United States.
Department of Biology, University of Virginia, Charlottesville, United States.
Elife. 2019 May 29;8:e45181. doi: 10.7554/eLife.45181.
Thyroid hormone (TH) regulates diverse developmental events and can drive disparate cellular outcomes. In zebrafish, TH has opposite effects on neural crest derived pigment cells of the adult stripe pattern, limiting melanophore population expansion, yet increasing yellow/orange xanthophore numbers. To learn how TH elicits seemingly opposite responses in cells having a common embryological origin, we analyzed individual transcriptomes from thousands of neural crest-derived cells, reconstructed developmental trajectories, identified pigment cell-lineage specific responses to TH, and assessed roles for TH receptors. We show that TH promotes maturation of both cell types but in distinct ways. In melanophores, TH drives terminal differentiation, limiting final cell numbers. In xanthophores, TH promotes accumulation of orange carotenoids, making the cells visible. TH receptors act primarily to repress these programs when TH is limiting. Our findings show how a single endocrine factor integrates very different cellular activities during the generation of adult form.
甲状腺激素 (TH) 调节多种发育事件，并能驱动不同的细胞结果。在斑马鱼中，TH 对成年条纹模式的神经嵴衍生色素细胞有相反的作用，限制黑素细胞群体的扩张，但增加黄色/橙色黄色素细胞的数量。为了了解 TH 如何在具有共同胚胎起源的细胞中引发看似相反的反应，我们分析了来自数千个神经嵴衍生细胞的单个转录组，重建了发育轨迹，鉴定了 TH 对色素细胞谱系的特异性反应，并评估了 TH 受体的作用。我们表明，TH 以不同的方式促进两种细胞类型的成熟。在黑素细胞中，TH 驱动终末分化，限制最终细胞数量。在黄色素细胞中，TH 促进橙色类胡萝卜素的积累，使细胞可见。当 TH 受到限制时，TH 受体主要作用是抑制这些程序。我们的发现表明，在生成成年形态的过程中，单一的内分泌因子如何整合非常不同的细胞活动。
