Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells
- Carnegie Mellon University, United States
- Universiti Sains Malaysia, Malaysia
- University of Pittsburgh, United States
- Boston University, United States
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 (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.
Data availability
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.
Article and author information
Author details
Funding
Samuel & Emma Winters Foundation (A025662)
- Xi Ren
Carnegie Mellon University
- Xi Ren
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Paul W Noble, Cedars-Sinai Medical Centre, United States
Version history
- Received: February 25, 2021
- Preprint posted: March 3, 2021 (view preprint)
- Accepted: January 7, 2022
- Accepted Manuscript published: January 12, 2022 (version 1)
- Version of Record published: February 15, 2022 (version 2)
Copyright
© 2022, Ng et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells
eLife 11:e67872.
https://doi.org/10.7554/eLife.67872
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