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.

RNA 修饰被称为“表观转录组”，代表了影响间充质干细胞 (MSC) 中多种生物过程的关键调控层。这些由特定酶（通常称为“写入器”、“读取器”和“擦除器”）催化的修饰可以动态改变 MSC 的转录组景观，从而调节细胞分化、增殖和对环境线索的反应。这些酶包括 METTL、IGF2BP、WTAP、YTHD、FTO、NAT 等类别的成员。许多这些 RNA 修饰剂在 MSC 谱系分化过程中具有活性。这篇综述全面概述了目前对 MSC 中不同 RNA 修饰的理解、它们在调节干细胞行为中的作用以及它们对基于 MSC 的治疗的影响。它深入研究了 RNA 修饰如何影响 MSC 生物学、单个修饰的功能意义以及这些修饰之间复杂的相互作用。我们进一步讨论这些复杂的调节机制如何促进间充质干细胞的功能多样性，以及如何将它们用于治疗应用。该综述还强调了 MSC 中 RNA 修饰研究当前的挑战和潜在的未来方向，强调需要创新工具来精确绘制这些修饰并破译它们的特定效应。总的来说，这项工作为更深入地了解表观转录组在 MSC 生物学中的作用铺平了道路，有可能推进再生医学和基于 MSC 的疗法的治疗策略。