Abstract
Given the self-renewal, multi-differentiation, immunoregulatory, and tissue maintenance properties, mesenchymal stem cells (MSCs) are promising candidates for stem cell-based therapies. Breakthroughs have been made in uncovering MSCs as key contributors to homeostasis and the regenerative repair of tissues and organs derived from three germ layers. MSC differentiation into specialized cell types is sophisticatedly regulated, and accumulating evidence suggests long non-coding RNAs (lncRNAs) as the master regulators of various biological processes including the maintenance of homeostasis and multi-differentiation functions through epigenetic, transcriptional, and post-translational mechanisms. LncRNAs are ubiquitous and generally referred to as non-coding transcripts longer than 200 bp. Most lncRNAs are evolutionary conserved and species-specific; however, the weak conservation of their sequences across species does not affect their diverse biological functions. Although numerous lncRNAs have been annotated and studied, they are nevertheless only the tip of the iceberg; the rest remain to be discovered. In this review, we characterize MSC functions in homeostasis and highlight recent advances on the functions and mechanisms of lncRNAs in regulating MSC homeostasis and differentiation. We also discuss the current challenges and perspectives for understanding the roles of lncRNAs in MSC functions in homeostasis, which could help develop promising targets for MSC-based therapies.
Highlights
Mesenchymal stem cells (MSCs) are heterogeneous, multipotent adult stem cells that originate in the mesoderm and that have been isolated from diverse tissues such as adipose tissue, bone marrow, and umbilical cord
mesenchymal stem cells (MSCs) derived from patients with MM had abundant exosomal long non-coding RNAs (lncRNAs) RUNX2-AS1; further studies revealed that it could be transferred from MM cells to MSCs and thereby prevent MSC osteogenesis by downregulating RUNX2 (Li B. et al, 2018), which provides a novel pathological mechanism of the bone lesion in patients with MM and could be a potential therapeutic target in the future. These findings suggest that MSC-derived exosomes overexpressing lncRNAs such as H19 might be a novel direction for developing cell-free therapeutic strategies
LncRNAs have emerged as prominent modulators of MSC fate commitment and functional homeostasis (Table 1) through variable mechanisms (Figure 2)
Summary
Mesenchymal stem cells (MSCs) are heterogeneous, multipotent adult stem cells that originate in the mesoderm and that have been isolated from diverse tissues such as adipose tissue, bone marrow, and umbilical cord. MSCs themselves secrete abundant types of biofactors and extracellular vesicles (EVs) to potentially affect their surroundings, including supporting hematopoiesis and modulating immune responses (Wang et al, 2014; Kfoury and Scadden, 2015; Sui et al, 2020). These functional capabilities contribute to MSC modulation in tissue homeostasis. The regulation of MSC function in these processes is immensely complex and tightly controlled and warrants extensive studies
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