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 (mTs), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage mT 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.
All data supporting the findings of this study are available within the article and its supplementary files. Source data files have been provided for Figures 1 to 6.
- Xi Ren
- Xi Ren
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Paul W Noble, Cedars-Sinai Medical Centre, United States
- Received: February 25, 2021
- Accepted: January 7, 2022
- Accepted Manuscript published: January 12, 2022 (version 1)
© 2022, Ng et al.
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