Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Stem Cells. 2012 Nov;30(11):2487-97. doi: 10.1002/stem.1207.
The reproductive role of the fallopian tube is to transport the sperm and egg. The tube is positioned to act as a bridge between the ovary where the egg is released and the uterus where implantation occurs. Throughout reproductive years, the fallopian tube epithelium undergoes repetitive damage and regeneration. Although a reservoir of adult epithelial stem cells must exist to replenish damaged cells, they remain unidentified. Here, we report isolation of a subset of basally located human fallopian tube epithelia (FTE) that lack markers of ciliated (β-tubulin; TUBB4) or secretory (PAX8) differentiated cells. These undifferentiated cells expressed cell surface antigens: epithelial cell adhesion molecule, CD44, and integrin α 6. This FTE subpopulation was fivefold enriched for cells capable of clonal growth and self-renewal suggesting that they contain the FTE stem-like cells (FTESCs). A twofold enrichment of the FTESC was found in the distal compared to the proximal end of the tube. The distal fimbriated end of the fallopian tube is a well-characterized locus for initiation of serous carcinomas. An expansion of the cells expressing markers of FTESC was detected in tubal intraepithelial carcinomas and in fallopian tubes from patients with invasive serous cancer. These findings suggest that FTESC may play a role in the initiation of serous tumors. Characterization of these stem-like cells will provide new insight into how the FTE regenerate, respond to injury, and may initiate cancer.
输卵管的生殖作用是运输精子和卵子。输卵管的位置使其成为卵巢(卵子释放的地方)和子宫(着床发生的地方)之间的桥梁。在生殖期,输卵管上皮经历反复的损伤和再生。尽管必须存在储存成人上皮干细胞来补充受损细胞,但它们仍未被识别。在这里,我们报告了从人输卵管上皮(FTE)中分离出一组基底定位的细胞亚群,这些细胞缺乏纤毛(β-微管蛋白;TUBB4)或分泌(PAX8)分化细胞的标志物。这些未分化的细胞表达细胞表面抗原:上皮细胞黏附分子、CD44 和整合素α6。这个 FTE 亚群中能够克隆生长和自我更新的细胞富集了五倍,这表明它们包含 FTE 干细胞样细胞(FTESCs)。与输卵管近端相比,FTESC 在输卵管远端的丰度增加了两倍。输卵管的远端伞状末端是起始浆液性癌的特征性部位。在输卵管上皮内癌和侵袭性浆液性癌患者的输卵管中,检测到表达 FTESC 标志物的细胞扩张。这些发现表明,FTESC 可能在浆液性肿瘤的起始中发挥作用。对这些干细胞样细胞的特征描述将为了解 FTE 如何再生、对损伤作出反应以及可能引发癌症提供新的见解。