Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
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DOI：
10.3390/cancers12030694
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发表时间：
2020-03-01
期刊：
影响因子：
5.2
通讯作者：
Hippo, Yoshitaka
中科院分区：
文献类型：
--
作者：
Maru, Yoshiaki;Kawata, Akira;Hippo, Yoshitaka
子宫颈转化带（TZ）的化生上皮（包括鳞状柱交界处（SCJ））是人乳头瘤病毒（HPV）感染和随后癌症发展的主要目标。然而，由于缺乏足够的体外SCJ模型，对其生理作用和致癌性的研究受到限制。通过基于矩阵的三维培养技术，我们繁殖了来自正常SCJ区域的类器官，以及TZ中的化生鳞状细胞。类器官主要由鳞状细胞组成，结构致密。然而，至少在某些类器官中，一小群产生黏液的宫颈内细胞与鳞状细胞群相邻共存，实际上再现了TZ背景下SCJ的结构。此外，转录组分析证实，与非SCJ来源的永生化宫颈细胞系相比，许多SCJ标记基因在类器官中的表达水平更高。因此，获得的类器官似乎模仿宫颈SCJ细胞，特别是来自TZ的化生鳞状细胞，可能提供了一个新的平台，可以研究hpv驱动的宫颈癌发展。
The metaplastic epithelium of the transformation zone (TZ) including the squamocolumnar junction (SCJ) of the uterine cervix is a prime target of human papilloma virus (HPV) infection and subsequent cancer development. Due to the lack of adequate in vitro models for SCJ, however, investigations into its physiological roles and vulnerability to carcinogenesis have been limited. By using Matrigel-based three-dimensional culture techniques, we propagated organoids derived from the normal SCJ region, along with metaplastic squamous cells in the TZ. Consisting predominantly of squamous cells, organoids basically exhibited a dense structure. However, at least in some organoids, a small but discrete population of mucin-producing endocervix cells co-existed adjacent to the squamous cell population, virtually recapitulating the configuration of SCJ in a TZ background. In addition, transcriptome analysis confirmed a higher expression level of many SCJ marker genes in organoids, compared to that in the immortalized cervical cell lines of non-SCJ origin. Thus, the obtained organoids appear to mimic cervical SCJ cells and, in particular, metaplastic squamous cells from the TZ, likely providing a novel platform in which HPV-driven cervical cancer development could be investigated.