正常的发育进程依赖于前期和胚胎转移概念中胚胎和胚外谱系之间的密切相互作用。例如，小鼠外胚层来源的FGF和NODAL信号在胚外胚外胚层滋养层细胞中维持干细胞状态中起关键作用，而腹膜内胚层信号对于模式化外胚层前区的上皮胚层至关重要。这些发育阶段也与首个心脏前体的特定化有关。在这里，我们建立了一个稳定的小鼠胚胎干细胞向包含心肌细胞的胚胎体的分化方案，用于检验滋养层对此关键发育过程的影响。使用滋养层干细胞（TSCs）来产生滋养层调节培养基（TCM），我们表明TCM能够深入地减缓心肌细胞分化的动力学，并特异性地延迟心肌间叶祖细胞的出现。TCM还能强烈促进多能转录因子的保留，从而维持ESC的干细胞状态。通过应用来自不同突变的TSCs的TCM，我们进一步表明那些在体内对早期心脏发育有滋养层介导效应的突变会改变正常心肌细胞分化的轨迹。我们的方法有助于深入解析胚胎和胚外组织之间复杂的相互作用。它们证明滋养层有助于延长胚胎细胞的多能状态并延迟早期分化过程，很可能是通过产生白血病抑制因子（LIF）实现的。这些数据扩展了我们对早期胚胎不同组织间多面信号相互作用的了解，这些洞察对合成胚胎研究领域具有重要意义。

Normal developmental progression relies on close interactions between the embryonic and extraembryonic lineages in the pre- and peri-gastrulation stage conceptus. For example, mouse epiblast-derived FGF and NODAL signals are required to maintain a stem-like state in trophoblast cells of the extraembryonic ectoderm, while visceral endoderm signals are pivotal to pattern the anterior region of the epiblast. These developmental stages also coincide with the specification of the first heart precursors. Here, we established a robust differentiation protocol of mouse embryonic stem cells (ESCs) into cardiomyocyte-containing embryoid bodies that we used to test the impact of trophoblast on this key developmental process. Using trophoblast stem cells (TSCs) to produce trophoblast-conditioned medium (TCM), we show that TCM profoundly slows down the cardiomyocyte differentiation dynamics and specifically delays the emergence of cardiac mesoderm progenitors. TCM also strongly promotes the retention of pluripotency transcription factors, thereby sustaining the stem cell state of ESCs. By applying TCM from various mutant TSCs, we further show that those mutations that cause a trophoblast-mediated effect on early heart development in vivo alter the normal cardiomyocyte differentiation trajectory. Our approaches provide a meaningful deconstruction of the intricate crosstalk between the embryonic and the extraembryonic compartments. They demonstrate that trophoblast helps prolong a pluripotent state in embryonic cells and delays early differentiative processes, likely through production of leukemia inhibitory factor (LIF). These data expand our knowledge of the multifaceted signaling interactions among distinct compartments of the early conceptus that ensure normal embryogenesis, insights that will be of significance for the field of synthetic embryo research.