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bioRxiv · 10.1101/2021.03.03.433714

Recapitulate Human Cardio-pulmonary Co-development Using Simultaneous Multilineage Differentiation of Pluripotent Stem Cells

Ng, W. H.·Johnston, E. K.·Tan, J. J.·Bliley, J. M.·Feinberg, A. W.·Stolz, D. B.·Sun, M.·Hawkins, F.·Kotton, D. N.·Ren, X.
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Abstract

The extensive crosstalk between the developing heart and lung is pivotal for their proper morphogenesis and maturation. However, there remains a lack of model systems for investigating the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human pluripotent stem cells (hPSCs) via temporal specific tuning of WNT and TGF-{beta} signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (Ts), and observed expedited alveolar maturation in the presence of cardiac accompany. 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 our multilineage differentiation model to offer an experimentally tractable system for investigating human cardio-pulmonary interplay and tissue boundary formation during embryogenesis.

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Ng, W. H., Johnston, E. K., Tan, J. J., Bliley, J. M., Feinberg, A. W., Stolz, D. B., Sun, M., Hawkins, F., Kotton, D. N., Ren, X.. 2021-03-03. Recapitulate Human Cardio-pulmonary Co-development Using Simultaneous Multilineage Differentiation of Pluripotent Stem Cells. https://doi.org/10.1101/2021.03.03.433714

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