Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, United States.
Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia.
Elife. 2022 Jan 12;11:e67872. doi: 10.7554/eLife.67872.
The extensive crosstalk between the developing heart and lung is critical to their proper morphogenesis and maturation. However, there remains a lack of models that investigate the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing the simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human-induced pluripotent stem cells (hiPSCs) via temporal specific tuning of WNT and nodal signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (μTs), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage μT effectively segregated from each other with concurrent initiation of cardiac contraction. We expect that our multilineage differentiation model will offer an experimentally tractable system for investigating human cardio-pulmonary interaction and tissue boundary formation during embryogenesis.
心脏和肺之间的广泛串扰对于它们的正常形态发生和成熟至关重要。然而，目前仍然缺乏模型来研究人类胚胎发生过程中关键的心肺相互作用。在这里，我们报道了一种新的逐步策略，通过在没有外源性生长因子的情况下，通过时间特异性调节 WNT 和 nodal 信号，在单个诱导多能干细胞（hiPSC）分化中同时诱导中胚层来源的心脏和内胚层来源的肺上皮谱系。使用 3D 悬浮培养，我们建立了同心心肺微组织（μT），并在心脏伴随的情况下加速肺泡成熟。在撤回 WNT 激动剂后，每个双谱系μT 中的心脏和肺部分有效地彼此分离，同时启动心脏收缩。我们预计我们的多谱系分化模型将为研究人类心肺相互作用和组织边界形成提供一个可行的实验系统。
