Quantitative Clonal Analysis and Single-Cell Transcriptomics Reveal Division Kinetics, Hierarchy, and Fate of Oral Epithelial Progenitor Cells
Quantitative Clonal Analysis and Single-Cell Transcriptomics Reveal Division Kinetics, Hierarchy, and Fate of Oral Epithelial Progenitor Cells
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DOI：
10.1016/j.stem.2018.10.015
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发表时间：
2019-01-03
期刊：
影响因子：
23.9
通讯作者：
Klein, Ophir D.
中科院分区：
文献类型：
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作者：
Jones, Kyle B.;Furukawa, Sachiko;Klein, Ophir D.
口腔粘膜是身体中分裂最快的组织之一，并且充当对来自咀嚼、食物和微生物的物理和化学损伤的屏障。这一屏障的破坏可导致患者的显著发病率和潜在的危及生命的感染。因此，确定口腔上皮祖细胞（OEPCs）的身份和组织对于了解它们在体内平衡和疾病中的作用至关重要。使用谱系追踪和标签保留实验，我们表明，快速分裂的OEPCs广泛位于整个口腔粘膜的基底层内。定量克隆分析表明，OEPCs进行人口不对称分裂后中性漂移动力学，它们响应化疗诱导的损伤，通过改变子细胞的命运。最后，使用单细胞RNA-seq，我们建立了基底层群体结构，并提出了一个定义基底层内细胞组织的模型。
The oral mucosa is one of the most rapidly dividing tissues in the body and serves as a barrier to physical and chemical insults from mastication, food, and microorganisms. Breakdown of this barrier can lead to significant morbidity and potentially life-threatening infections for patients. Determining the identity and organization of oral epithelial progenitor cells (OEPCs) is therefore paramount to understanding their roles in homeostasis and disease. Using lineage tracing and label retention experiments, we show that rapidly dividing OEPCs are located broadly within the basal layer of the mucosa throughout the oral cavity. Quantitative clonal analysis demonstrated that OEPCs undergo population-asymmetrical divisions following neutral drift dynamics and that they respond to chemotherapy-induced damage by altering daughter cell fates. Finally, using single-cell RNA-seq, we establish the basal layer population structure and propose a model that defines the organization of cells within the basal layer.