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Effect and mechanism of hypoxia on differentiation of porcine-induced pluripotent stem cells into vascular endothelial cells

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Abstract

Pigs are similar to humans in organ size and physiological function, and are considered as good models for studying cardiovascular diseases. The study of porcine-induced pluripotent stem cells (piPSC) differentiating into vascular endothelial cells (EC) is expected to open up a new way of obtaining high-quality seed cells. Given that the hypoxic environment has an important role in the differentiation process of vascular EC, this work intends to establish a hypoxia-induced differentiation system of piPSC into vascular EC. There is evidence that the hypoxia microenvironment in the initial stage could significantly improve differentiation efficiency. Further study suggests that the hypoxia culture system supports a combined effect of hypoxia inducible factors and their associated regulatory molecules, such as HIF-1α, VEGFA, FGF2, LDH-A, and PDK1, which can efficiently promote the lineage-specific differentiation of piPSC into EC. Most notably, the high level of ETV2 after 4 d of hypoxic treatment indicates that it possibly plays an important role in the promoting process of EC differentiation. The research is expected to help the establishment of new platforms for piPSC directional induction research, so as to obtain adequate seed cells with ideal phenotype and functionality.

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Data availability

The data presented in this study are available upon request from the corresponding authors.

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Funding

This work was supported by the National Natural Science Foundation of China (22007010), and the Provincial University Collaborative Innovation Achievement Project (LJGXCG2023-057).

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Author notes

  1. Yimei Li and Danyang Song contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Animal Cellular and Genetic Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin, 150030, Heilongjiang, China

    Yimei Li, Danyang Song, Zhuoran Yu, Yu Zhang, Zhonghua Liu & Tingsheng Yan

  2. College of Life Science, Northeast Agricultural University, Harbin, 150030, China

    Yimei Li, Danyang Song, Zhuoran Yu, Zhonghua Liu & Tingsheng Yan

  3. School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an 710061, China

    Yu Zhang

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  1. Yimei Li
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Contributions

Conceptualization and methodology, Y.L. and T.Y.; software, Y.L., D.S., and Z.Y.; validation, Y.L., D.S., and Z.Y.; formal analysis, investigation, resources data and curation, Y.L., D.S., Z.Y., Y.Z., Z.L., and T.Y.; writing–original draft preparation, Y.L., Y.Z., and T.Y.; writing–review and editing, Y.L., D.S., and T.Y.; visualization, D.S. and T.S.; supervision, Z.L.; project administration, Y.Z., Z.L., and T.Y.; funding acquisition, T.Y. All the authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Tingsheng Yan.

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Ethics approval

All animal experiments were approved by Animal Care and Use Committee of Northeast Agricultural University and Animal Care and Use Committee of Northeast Agricultural University and were performed according to the guidelines for the welfare and use of animals in stem cell research. The study was approved by the Ethics Committee of Northeast Agriculture University (protocol code: NEAUEC20).

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The authors declare no competing interests.

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Li, Y., Song, D., Yu, Z. et al. Effect and mechanism of hypoxia on differentiation of porcine-induced pluripotent stem cells into vascular endothelial cells. In Vitro Cell.Dev.Biol.-Animal 60, 9–22 (2024). https://doi.org/10.1007/s11626-023-00833-8

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