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Epitranscriptomic modifications in mesenchymal stem cell differentiation: advances, mechanistic insights, and beyond

Cell Death & Differentiation volume 31, pages 9–27 (2024)Cite this article

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Abstract

RNA modifications, known as the “epitranscriptome”, represent a key layer of regulation that influences a wide array of biological processes in mesenchymal stem cells (MSCs). These modifications, catalyzed by specific enzymes, often termed “writers”, “readers”, and “erasers”, can dynamically alter the MSCs’ transcriptomic landscape, thereby modulating cell differentiation, proliferation, and responses to environmental cues. These enzymes include members of the classes METTL, IGF2BP, WTAP, YTHD, FTO, NAT, and others. Many of these RNA-modifying agents are active during MSC lineage differentiation. This review provides a comprehensive overview of the current understanding of different RNA modifications in MSCs, their roles in regulating stem cell behavior, and their implications in MSC-based therapies. It delves into how RNA modifications impact MSC biology, the functional significance of individual modifications, and the complex interplay among these modifications. We further discuss how these intricate regulatory mechanisms contribute to the functional diversity of MSCs, and how they might be harnessed for therapeutic applications. The review also highlights current challenges and potential future directions in the study of RNA modifications in MSCs, emphasizing the need for innovative tools to precisely map these modifications and decipher their context-specific effects. Collectively, this work paves the way for a deeper understanding of the role of the epitranscriptome in MSC biology, potentially advancing therapeutic strategies in regenerative medicine and MSC-based therapies.

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Fig. 1: Origin, characteristics, therapeutic strategies, and applications of MSCs.
Fig. 2: Types of RNA modifications and their influential role in RNA metabolism.
Fig. 3: Influences of RNA modification on osteogenic differentiation of MSCs.
Fig. 4: The pivotal role of RNA modifications in MSC adipogenic differentiation.
Fig. 5: Role of RNA modifications in other lineage-specific differentiations of MSCs.
Fig. 6: RNA modifications and their impact on MSCs proliferation, self-renewal, migration, and senescence.
Fig. 7: Role of RNA modifications in MSC paracrine signaling.

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Funding

Funding

This work was supported by National Natural Science Foundation of China (81901006, 82372905), Young Top-notch Talent of Pearl River Talent Plan (0920220228), Guangdong Provincial Science and Technology Project Foundation (2022A0505050038), Scientific Research Talent Cultivation Project of Stomatological Hospital, Southern Medical University (RC202005) and Science Research Cultivation Program of Stomatological Hospital, Southern Medical University (PY2020002).

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Author notes

  1. These authors contributed equally: Jiarong Zheng, Ye Lu.

Authors and Affiliations

  1. Department of Dentistry, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Jiarong Zheng & Bing Guo

  2. Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China

    Jiarong Zheng, Ye Lu, Yunfan Lin, Shanshan Si, Xinyuan Zhao & Li Cui

  3. Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, 90095, CA, USA

    Li Cui

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  1. Jiarong Zheng
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Contributions

LC, BG. and XZ conceptualized the idea of the review. LC, JZ and YL prepared initial drafts of the manuscript. LC, BG, XZ, YFL, and SS contributed to the writing, graph creation and manuscript improvement. JZ, YL contributed to the creation of graphs, tables. All authors reviewed the manuscript and approved to the final version of this manuscript.

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Correspondence to Bing Guo, Xinyuan Zhao or Li Cui.

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Zheng, J., Lu, Y., Lin, Y. et al. Epitranscriptomic modifications in mesenchymal stem cell differentiation: advances, mechanistic insights, and beyond. Cell Death Differ 31, 9–27 (2024). https://doi.org/10.1038/s41418-023-01238-6

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  • DOI: https://doi.org/10.1038/s41418-023-01238-6

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