Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
Int J Biol Sci. 2024 Sep 23;20(13):5056-5069. doi: 10.7150/ijbs.99519. eCollection 2024.
It has been reported that human embryonic stem cells (hESCs) treated with BMP4 and inhibitors of TGFβ signaling (A83-01) and FGF signaling (PD173074), called BAP, can efficiently differentiate to extraembryonic (ExE) cells . Due to restricted access to human embryos, it is ethically impossible to test the developmental potential of ExE cells . Here, we demonstrate that most ExE cells expressed molecular markers for both trophoblasts (TBs) and amniotic cells (ACs). Following intra-uterine transplantation, ExE cells contributed to the mouse placenta. More interestingly, ExE cells could chimerize with the mouse blastocyst as, after injection into the blastocyst, they penetrated its trophectoderm. After implantation of the injected blastocysts into surrogate mice, human cells were found at E14 in placental labyrinth, junction zones, and even near the uterine decidua, expressed placental markers, and secreted human chorionic gonadotropin. Surprisingly, ExE cells also contributed to cartilages of the chimeric embryo with some expressing the chondrogenic marker SOX9, consistent with the mesodermal potential of TBs and ACs in the placenta. Deleting , a mesodermal determinant, restricted the contribution of ExE cells to the placenta. Thus, we conclude that hESC-derived ExE cells can chimerize with the mouse blastocyst and contribute to both the placenta and cartilages of the chimera consistent with their heteogenious nature. Intra-uterus and intra-blastocyst injections are novel and sensitive methods to study the developmental potential of ExE cells.
据报道，用 BMP4 和 TGFβ 信号通路抑制剂（A83-01）和 FGF 信号通路抑制剂（PD173074）处理的人胚胎干细胞（hESCs），称为 BAP，可以有效地分化为胚外细胞（ExE）。由于人类胚胎的获取受到限制，因此从伦理角度来看，不可能测试 ExE 细胞的发育潜能。在这里，我们证明大多数 ExE 细胞表达滋养层（TBs）和羊水细胞（ACs）的分子标记物。在宫内移植后，ExE 细胞有助于形成胎盘。更有趣的是，ExE 细胞可以与小鼠囊胚嵌合，因为将其注入囊胚后，它们可以穿透其滋养外胚层。将注射的囊胚植入代孕小鼠后，在胎盘绒毛膜、连接区，甚至在靠近子宫蜕膜处发现了人类细胞，表达胎盘标记物，并分泌人绒毛膜促性腺激素。令人惊讶的是，ExE 细胞还可以参与嵌合体胚胎的软骨形成，其中一些细胞表达软骨形成标记物 SOX9，与胎盘 TBs 和 ACs 的中胚层潜能一致。删除中胚层决定因子，限制了 ExE 细胞对胎盘的贡献。因此，我们得出结论，hESC 衍生的 ExE 细胞可以与小鼠囊胚嵌合，并有助于形成胎盘和嵌合体的软骨，这与它们的异质性性质一致。子宫内和囊胚内注射是研究 ExE 细胞发育潜能的新的、敏感的方法。
