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Using single-cell RNA sequencing to unravel cell lineage relationships in the respiratory tract.

使用单细胞 RNA 测序解开呼吸道中的细胞谱系关系。

  • 影响因子:4.04
  • DOI:10.1042/BST20191010
  • 作者列表:"Zaragosi LE","Deprez M","Barbry P
  • 发表时间:2020-01-10
Abstract

:The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

摘要

: 呼吸道由从鼻子到终末细支气管的假复层上皮排列。肺对外界应激的第一道防线包括 5 种主要的细胞类型: 基底细胞、杯状细胞和多核细胞,以及稀有细胞如离子细胞、神经内分泌和簇/刷细胞。在稳态时,这种上皮以较低的速率自我更新,但在损伤时能够快速再生。通过基因标记研究了小鼠再生过程中的气道上皮细胞谱系,主要是在有害物质损伤上皮后。从这些方法中,基底细胞已被确定为棒状细胞、杯状细胞和多面细胞的祖细胞,但也有离子细胞和神经内分泌细胞的祖细胞。单细胞 RNA 测序,再加上谱系推断算法,已经独立地允许在小鼠和人类中建立细胞谱系关系的综合图片。与小鼠气管中的遗传示踪实验一致,使用单细胞 RNA 测序 (RNAseq) 的研究表明,基底细胞首先分化为棒状细胞, 从而成熟成杯状细胞或分化成多个细胞。在人气道上皮中,单细胞 RNAseq 已经鉴定出新的中间群体,如氘代小细胞、 '杂交' 的粘液多融合细胞和稀有细胞的祖细胞。还发现了新的分化动力学,如从杯状细胞向多聚细胞的转变。呼吸道细胞谱系关系的未来现在在于基因标记方法与单细胞 RNAseq 的结合,以明确的方式建立, 正常和病理情况下细胞谱系的标志。

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关键词: 暂无
翻译标题与摘要 下载文献
影响因子:3.94
发表时间:2020-01-15
DOI:10.1016/j.taap.2019.114847
作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:4.04
发表时间:2020-01-10
DOI:10.1042/BST20191010
作者列表:["Zaragosi LE","Deprez M","Barbry P"]

METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

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