Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells

Authors : Wai Hoe Ng, Elizabeth K Johnston, Jun Jie Tan, Jacqueline M Bliley, Adam W Feinberg, Donna B Stolz, Ming Sun, Piyumi Wijesekara, Finn Hawkins, Darrell N Kotton, Xi Ren

Title of Publication : Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells

Journal Name : ELIFE

Quartile : Q1

Impact Factor : 8.146

Link : https://elifesciences.org/articles/67872

Description : 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 (?Ts), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage ?T 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.