Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK.
Centre for Trophoblast Research, Tennis Court Road, University of Cambridge, Cambridge CB2 3DY, UK.
Development. 2018 Apr 16;145(16):dev162305. doi: 10.1242/dev.162305.
During pregnancy the trophoblast cells of the placenta are the only fetal cells in direct contact with maternal blood and decidua. Their functions include transport of nutrients and oxygen, secretion of pregnancy hormones, remodelling of the uterine arteries, and communicating with maternal cells. Despite the importance of trophoblast cells in placental development and successful pregnancy, little is known about the identity, location and differentiation of human trophoblast progenitors. We identify a proliferative trophoblast niche at the base of the cytotrophoblast cell columns in first trimester placentas that is characterised by integrin α2 (ITGA2) expression. Pulse-chase experiments with 5-iodo-2'-deoxyuridine indicate that these cells might contribute to both villous (VCT) and extravillous (EVT) lineages. These proliferating trophoblast cells can be isolated by flow cytometry using ITGA2 as a marker and express genes from both VCT and EVT. Microarray expression analysis shows that ITAG2 cells display a unique transcriptional signature, including genes involved in NOTCH signalling, and exhibit a combination of epithelial and mesenchymal characteristics. ITGA2 thus marks a niche allowing the study of pure populations of trophoblast progenitor cells.
在妊娠期间,胎盘的滋养层细胞是唯一与母体血液和蜕膜直接接触的胎儿细胞。它们的功能包括运输营养物质和氧气、分泌妊娠激素、重塑子宫动脉以及与母体细胞进行通讯。尽管滋养层细胞在胎盘发育和成功妊娠中非常重要,但对于人类滋养层祖细胞的身份、位置和分化知之甚少。我们在早期胎盘的细胞滋养层细胞柱的底部鉴定出一个增殖性滋养层生态位,其特征在于整合素 α2(ITGA2)的表达。用 5-碘-2'-脱氧尿苷进行脉冲追踪实验表明,这些细胞可能有助于绒毛(VCT)和绒毛外(EVT)谱系。这些增殖的滋养层细胞可以使用 ITGA2 作为标记通过流式细胞术分离,并且表达来自 VCT 和 EVT 的基因。微阵列表达分析表明,ITAG2 细胞显示出独特的转录特征,包括涉及 NOTCH 信号通路的基因,并表现出上皮和间充质特征的组合。因此,ITGA2 标志着一个允许研究纯滋养层祖细胞群体的生态位。