Epigenetic Regulation of Mesenchymal Stem Cell Homeostasis

Epigenetic marks, enzymatic regulators, and noncoding RNAs modulate fate decisions and functional homeostasis of MSCs for the maintenance of tissue health. Increasing evidence suggests that epigenetic dysregulation is a key contributor to MSC dysfunction and to subsequent age-related and disease-associated tissue deterioration. Recent studies have demonstrated that epigenetic mechanisms support MSC-mediated tissue regeneration through cell transplantation-based or pharmacology-based therapeutics. A better understanding of the epigenetic regulation of MSC homeostasis will provide novel insights into how stem cells are regulated in vivo and how organismal health is established and maintained. Mesenchymal stem cells (MSCs) have putative roles in maintaining adult tissue health, and the functional decline of MSCs has emerged as a crucial pathophysiological driver of various diseases. Epigenetic regulation is essential for establishing and preserving MSC homeostasis in vivo. Furthermore, growing evidence suggests that epigenetic dysregulation contributes to age- and disease-associated MSC alterations. Epigenetic marks in MSCs can be amplified through self-renewal divisions and transmitted to differentiated progeny, further perpetuating their role in tissue maintenance and pathogenesis. We review the epigenetic regulation of MSC homeostasis, emphasizing its contributions to organismal health and disease. Understanding these epigenetic mechanisms could hold promise as targets for MSC-mediated regenerative therapies. Mesenchymal stem cells (MSCs) have putative roles in maintaining adult tissue health, and the functional decline of MSCs has emerged as a crucial pathophysiological driver of various diseases. Epigenetic regulation is essential for establishing and preserving MSC homeostasis in vivo. Furthermore, growing evidence suggests that epigenetic dysregulation contributes to age- and disease-associated MSC alterations. Epigenetic marks in MSCs can be amplified through self-renewal divisions and transmitted to differentiated progeny, further perpetuating their role in tissue maintenance and pathogenesis. We review the epigenetic regulation of MSC homeostasis, emphasizing its contributions to organismal health and disease. Understanding these epigenetic mechanisms could hold promise as targets for MSC-mediated regenerative therapies. a single-stranded RNA that forms a closed continuous loop and operates as a noncoding RNA to regulate gene expression at the transcriptional or post-transcriptional levels. an RNA that acts as a molecular sponge for miRNAs, thereby derepressing miRNA target genes at the post-transcriptional level. regions of DNA enriched in cytosine–guanine dinucleotides. DNA methylation occurs very commonly on cytosines in CpG sites. epigenetic marks or effects that are poorly regulated owing to the altered expression or activity of epigenetic enzymes or noncoding RNAs in pathophysiological disorders. lipid bilayer-delimited particles that are released from a cell. EVs carry cargos including proteins and nucleic acids for intercellular communication. EVs can be broadly classified into exosomes, microvesicles, and apoptotic bodies according to their origin and size. a tightly packed form of DNA which is marked by repressive H3K9 methylation and is involved in stable inactivation of gene transcription. RNA transcripts >200 nt in length that are not translated into protein. lncRNAs can regulate gene expression at the transcriptional or post-transcriptional levels via multiple mechanisms. a serine/threonine kinase signaling pathway that senses environmental and cellular energy status, and further regulates mammalian metabolism and stem cell function. small noncoding RNA molecules ∼22 nt in length that function via base-pairing to complementary sequences in mRNA targets, leading to RNA silencing or translation inhibition. the state of MSCs in which they maintain a relatively stable capacity to proliferate, differentiate, and support niche components according to tissue health demands. the potential of stem cells to give rise to specialized cell types of several lineages following specific stimuli. a polycomb group (PcG) protein complex that binds to H3K27me3 and catalyzes ubiquitination of histone H2A, leading to gene silencing. a PcG protein complex that has histone methyltransferase activity and primarily catalyzes the formation of H3K27me3, a mark of transcriptionally silent chromatin. the process by which stem cells divide and proliferate to expand the population while maintaining an undifferentiated state, thus perpetuating the stem cell pool throughout life. the state during which cells stop dividing and enter growth arrest without undergoing cell death. the microenvironment within a specific anatomic location where stem cells reside and receive cues that regulate their fate. the ability of stem cells to replicate themselves, to differentiate into other types of cells, and to interact with the microenvironment. a diverse family of epigenetic modifiers that catalyze H3K4 methylation to promote gene transcription; TrxG proteins act antagonistically to PcG proteins. a group of signal transduction pathways activated by binding of a Wnt protein ligand to its surface receptor. The canonical Wnt pathway regulates gene transcription and modulates stem cell function.