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

Using single-cell RNA sequencing to unravel cell lineage relationships in the respiratory tract.
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使用单细胞 RNA 测序来揭示呼吸道中的细胞谱系关系。

DOI:
10.1042/bst20191010
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发表时间:
2020
影响因子:
3.9
通讯作者:
Pascal Barbry
Pascal Barbry
中科院分区:
生物学3区
文献类型:
--
作者:
L. Zaragosi;Marie Deprez;Pascal Barbry

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呼吸道从鼻到终末细支气管由假复层上皮覆盖。肺抵抗外部压力的第一道防线包括五种主要细胞类型:基底细胞、基底上细胞、棒状细胞、杯状细胞和多纤毛细胞,以及稀有细胞,如离子细胞、神经内分泌细胞和丛状/刷状细胞。在体内平衡时,这种上皮以低速率自我更新,但在损伤时能够快速再生。通过基因标记研究了小鼠气道上皮细胞再生过程中的细胞谱系,主要是在用有毒物质损伤上皮后。从这些方法,基底细胞已被确定为俱乐部,杯状和多纤毛细胞的祖细胞,但也离子细胞和神经内分泌细胞。单细胞RNA测序,加上谱系推理算法,已经独立地允许建立小鼠和人类细胞谱系关系的全面图片。与小鼠气管中的遗传追踪实验一致,使用单细胞RNA测序(RNAseq)的研究表明,基底细胞首先分化为俱乐部细胞,然后成熟为杯状细胞或分化为多纤毛细胞。在人类气道上皮中,单细胞RNAseq已经鉴定出新的中间群体,如后体细胞、“杂交”粘液多纤毛细胞和罕见细胞的祖细胞。还发现了新的分化动力学,例如从杯状细胞到多纤毛细胞的转变。呼吸道中细胞谱系关系的未来现在取决于遗传标记方法与单细胞RNAseq的组合,以明确的方式建立正常和病理情况下细胞谱系的标志。
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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