Journal
SCIENTIFIC REPORTS
Volume 9, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-019-45047-9
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Funding
- Fundacao para a Ciencia e Tecnologia (FCT) Portugal [PD/BC128362/2017]
- FCT Portugal [PD/BD135500/2018]
- FCT Portugal through iBB, Institute for Bioengineering and Biosciences [UID/BIO/04565/2013]
- Programa Operacional Regional de Lisboa 2020 [007317]
- project PRECISE - Accelerating progress toward the new era of precision medicine [PAC-PRECISE-LISBOA-01-0145-FEDER-016394, SAICTPAC/0021/2015]
- European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant [739572 (H2020-WIDESPREAD-01-2016-2017)]
- [PTDC/EMD-TLM/29728/2017]
- [PTDC/EQU-EQU/29653/2017]
- Fundação para a Ciência e a Tecnologia [SAICTPAC/0021/2015, PTDC/EQU-EQU/29653/2017] Funding Source: FCT
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Human induced pluripotent stem cells (hiPSCs) represent an almost limitless source of cells for disease modelling and drug screening applications. Here we established an efficient and robust 3D platform for cardiomyocyte (CMs) production from hiPSCs, solely through small-molecule-based temporal modulation of the Wnt signalling, which generates more than 90% cTNT(+) cells. The impact of performing the differentiation process in 3D conditions as compared to a 2D culture system, was characterized by transcriptomic analysis by using data collected from sequential stages of 2D and 3D culture. We highlight that performing an initial period of hiPSC aggregation before cardiac differentiation primed hiPSCs towards an earlier mesendoderm lineage differentiation, via TGF-beta/Nodal signaling stabilization. Importantly, it was also found that CMs in the 3D microenvironment mature earlier and show an improved communication system, which we suggested to be responsible for a higher structural and functional maturation of 3D cardiac aggregates.
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