Arabpour Auriana, DiRusso Jonathan Adam, Wu Qiu Ya, Larsen Mark, Hwang Young Sun, Jacobson Elsie, Pham Thi Xuan Ai, Agranonik Nicole, Sparrow Megan, Monteiro Vernon Leander, Bian Zenya Rebecca, Pelaez-Restrepo Nicolas, Callejas-Marin Antuca, Pasque Vincent, Plath Kathrin, Clark Amander T
Dept. of Molecular, Cell, and Developmental Biology, University of California Los Angeles (UCLA); Los Angeles, CA 90095, USA.
Molecular Biology Institute, University of California Los Angeles (UCLA); Los Angeles CA 90095, USA.
bioRxiv. 2025 Jun 27:2025.06.26.661839. doi: 10.1101/2025.06.26.661839.
Amnion, germline and mesoderm specification at the posterior end of the human embryo occur around the same time . Similarly, generation of germline and amnion is associated with mesoderm induction regardless of differentiation platform. Yet, the lineage relationships between amnion, germline and mesoderm remains unresolved. By adding Basement Membrane Extract (BME) to the media, we demonstrate emergence of TFAP2A+/SOX2- epithelial progenitor cells which develop in response to BMP receptor signaling. We track the order of embryonic events that take place from this progenitor pool revealing that amnion-like cells (AMLCs) and primordial germ cell (PGC)-like cells (PGCLCs) are specified first. Shortly after, gastrulating mesoderm-like cells (MeLCs) arise that undergo an epithelial to mesenchymal transition (EMT). These results highlight the interconnected role of basement membrane deposition and BMP receptor signaling in the specification of human germline, amnion and mesoderm from TFAP2A+ embryonic progenitors.
羊膜、生殖系和中胚层在人类胚胎后端的特化大约在同一时间发生。同样,无论分化平台如何,生殖系和羊膜的产生都与中胚层诱导相关。然而,羊膜、生殖系和中胚层之间的谱系关系仍未明确。通过向培养基中添加基底膜提取物(BME),我们证明了TFAP2A+/SOX2-上皮祖细胞的出现,这些细胞是对BMP受体信号作出反应而发育的。我们追踪了从这个祖细胞库发生的胚胎事件顺序,发现首先特化出类羊膜细胞(AMLCs)和类原始生殖细胞(PGCLCs)。不久之后,出现了进行上皮-间充质转化(EMT)的原肠胚形成中胚层样细胞(MeLCs)。这些结果突出了基底膜沉积和BMP受体信号在从TFAP2A+胚胎祖细胞特化人类生殖系、羊膜和中胚层过程中的相互关联作用。