Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures
Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures
复制标题
DOI：
10.1242/dev.177428
复制
发表时间：
2019-10-01
期刊：
影响因子：
4.6
通讯作者：
Zaragosi, Laure-Emmanuelle
中科院分区：
文献类型：
--
作者：
Garcia, Sandra Ruiz;Deprez, Marie;Zaragosi, Laure-Emmanuelle
上呼吸道上皮细胞主要由多纤毛细胞、杯状细胞、棒状细胞和基底细胞组成，保证了正常的粘膜纤毛功能，并能在受到攻击时再生。在慢性气道疾病中，有缺陷的修复导致组织重塑。描述分化动力学的关键驱动因素可以帮助理解正常或病理性再生是如何发生的。使用单细胞转录组学和谱系推断，我们解开了从基底细胞到腔细胞的轨迹，为特定人群提供了新的标记。我们报告：（1）多纤毛细胞的前体亚群，我们称之为后体细胞，由特异性标记物定义，如DEUP 1、FOXN 4、YPEL 1、HES 6和CDC 20 B;（2）杯状细胞可以是多纤毛细胞的前体，从而解释了共表达杯状细胞和多纤毛细胞标记物的杂交细胞的存在;和（3）可以鉴定参与再生过程的分子库，例如角蛋白或Notch、Wnt或BMP/TGF β途径的组分。我们的结果对新鲜的人和猪的气道样本，小鼠气管细胞的确认，扩展和确认我们的结论，在工作中的分子和细胞的编排在粘膜纤毛上皮分化。
The upper airway epithelium, which is mainly composed of multiciliated, goblet, club and basal cells, ensures proper mucociliary function and can regenerate in response to assaults. In chronic airway diseases, defective repair leads to tissue remodeling. Delineating key drivers of differentiation dynamics can help understand how normal or pathological regeneration occurs. Using single-cell transcriptomics and lineage inference, we have unraveled trajectories from basal to luminal cells, providing novel markers for specific populations. We report that: (1) a precursor subgroup of multiciliated cells, which we have entitled deuterosomal cells, is defined by specific markers, such as DEUP1, FOXN4, YPEL1, HES6 and CDC20B; (2) goblet cells can be precursors of multiciliated cells, thus explaining the presence of hybrid cells that co-express markers of goblet and multiciliated cells; and (3) a repertoire of molecules involved in the regeneration process, such as keratins or components of the Notch, Wnt or BMP/TGF beta pathways, can be identified. Confirmation of our results on fresh human and pig airway samples, and on mouse tracheal cells, extend and confirm our conclusions regarding the molecular and cellular choreography at work during mucociliary epithelial differentiation.