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Derivation of Human Salivary Epithelial Progenitors from Pluripotent Stem Cells via Activation of RA and Wnt Signaling

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Abstract

Derivation of salivary gland epithelial progenitors (SGEPs) from human pluripotent stem cells (hPSCs) has great potential in developmental biology and regenerative medicine. At present, no efficient method is available to generate salivary gland cells from hPSCs. Here, we described for the first time a robust protocol for direct differentiation of hPSCs into SGEPs by mimicking retinoic acid and Wnt signaling. These hPSC-derived SGEPs expressed SOX9, KRT5, and KRT19, important progenitor markers of develo** salivary glands. CD24 and α-SMA positive cells, capable of restoring the functions of injured salivary glands, were also present in SGEP cultures. Importantly, RNA-sequencing revealed that the SGEPs resembled the transcript profiles of human fetal submandibular glands. Therefore, we provided an efficient protocol to induce hPSCs differentiation into SGEPs. Our study provides a foundation for generating functional hPSCs derived salivary gland acinar cells and three-dimensional organoids, potentially serving as new models for basic study and future translational research.

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Data Availability

The data used in this article will be available from the authors on reasonable request.

Code Availability

The RNA-seq data files in this paper have been deposited into Gene Expression Omnibus (GEO). The accession number is GEO: GSE198097.

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Acknowledgements

We thank the professor. Duanqin Pei of the Guangzhou Institutes of Biomedicine and Health kindly provides the hiPS cell lines. We also thank the professor. Yuanyuan Zhang of the Wake Forest Institute for Regenerative Medicine for the guidance of this work. Moreover, the authors thank National Center for Protein Sciences at Peking University in Bei**g, China, for assistance with providing Roche qPCR equipment and Nikon A1R confocal microscopy photography.

Funding

This work was supported by Discipline Development Fund of School of Stomatology, Peking University.

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Authors and Affiliations

  1. Central Laboratory, and Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology, Peking University, Bei**g, 100081, China

    Siqi Zhang, Yi Sui, Yifei Zhang, Shuang Yan, Chong Ding & Yanrui Feng

  2. Institute of Molecular Medicine, Peking University, Bei**g, 100871, China

    Siqi Zhang, **gwei **ong & Shicheng Wei

  3. Laboratory of Biomaterials and Regenerative Medicine, Academy for Advanced Interdisciplinary Studies, Peking University, Bei**g, 100871, China

    Shicheng Wei

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  1. Siqi Zhang
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Contributions

Conceptualization: S.Z., J.X. and S.W.; Methodology: S.Z., S.Y. and C.D.; Investigation: S.Z., Y.Z. and Y.F.; Formal Analysis: Y.Z. and S.Y.; Verification: S.Z., Y.S, and S.W.; Writing – Original Draft: S.Z., Y.S.; Writing – Review & Editing: Y.S., Y.Z., J.X., and S.W.; Resources: S.Z., Y.F.; Supervision: S.Z., S.W., and J.X.; Project Administration: S.Z., S.W.; Funding Acquisition: J.X., S.W.

Corresponding author

Correspondence to Shicheng Wei.

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Ethics Approval

This work involved isolation of embryonic mouse SMGs and adult human SMGs. All procedures performed in this study were reviewed and approved by the Biomedical Ethics Committee of Peking University in China. The permit number for the animal part is LA2021052. The permit number for the human part is 19093.

Consent to Participate

The human salivary gland tissues were collected after obtaining informed consent from the donors.

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Not applicable.

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No competing interests declared.

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Zhang, S., Sui, Y., Zhang, Y. et al. Derivation of Human Salivary Epithelial Progenitors from Pluripotent Stem Cells via Activation of RA and Wnt Signaling. Stem Cell Rev and Rep 19, 430–442 (2023). https://doi.org/10.1007/s12015-022-10431-y

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