Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation
Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation
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DOI：
10.1016/j.stemcr.2015.09.020
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发表时间：
2015-12-08
影响因子：
5.9
通讯作者：
Eaves, Connie J.
中科院分区：
文献类型：
--
作者：
Kang, Sung Yoon Catherine;Kannan, Nagarajan;Eaves, Connie J.
人腭扁桃体是口咽淋巴样组织，包含多个内陷（隐窝），其中外表面上皮的连续性被破坏，分离的上皮细胞与其他细胞类型混合。我们现在表明，在体外2D集落试验和3D培养系统中检测到的原始上皮细胞是CD44(+)NGFR(+)，并且存在于表面和隐窝区域。转录组分析表明，这两个区域的CD44(+)NGFR（+）细胞高度相似，尽管从隐窝分离的细胞含有较高比例的最原始（holo）克隆细胞。用人乳头瘤病毒16编码的E6/E7慢病毒转导这两个区域的CD44(+)NGFR（+）细胞可延长其在2D培养中的生长，并在3D培养中引起异常分化。因此，我们的研究结果揭示了正常人类扁桃体上皮祖细胞的共享、位点独立、等级组织、分化潜力和转录谱。他们还引入了一种新的模型来研究它们的转化机制。
Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44(+)NGFR(+) and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44(+)NGFR(+) cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44(+)NGFR(+) cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.