Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells
Year: 2022
Type: article
Abstract: 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.
Source: eLife
DOI: 10.7554/elife.67872
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
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4206283957