Epigenetic Regulators of Mesenchymal Stem/Stromal Cell Lineage Determination
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SKELETAL BIOLOGY AND REGULATION (M FORWOOD AND A ROBLING, SECTION EDITORS)
Epigenetic Regulators of Mesenchymal Stem/Stromal Cell Lineage Determination Dimitrios Cakouros 1,2 & Stan Gronthos 1,2
# The Author(s) 2020
Abstract Purpose of Review Although many signalling pathways have been discovered to be essential in mesenchymal stem/stromal (MSC) differentiation, it has become increasingly clear in recent years that epigenetic regulation of gene transcription is a vital component of lineage determination, encompassing diet, lifestyle and parental influences on bone, fat and cartilage development. Recent Findings This review discusses how specific enzymes that modify histone methylation and acetylation or DNA methylation orchestrate the differentiation programs in lineage determination of MSC and the epigenetic changes that facilitate development of bone related diseases such as osteoporosis. The review also describes how environmental factors such as mechanical loading influence the epigenetic signatures of MSC, and how the use of chemical agents or small peptides can regulate epigenetic drift in MSC populations during ageing and disease. Summary Epigenetic regulation of MSC lineage commitment is controlled through changes in enzyme activity, which modifies DNA and histone residues leading to alterations in chromatin structure. The co-ordinated epigenetic regulation of transcriptional activation and repression act to mediate skeletal tissue homeostasis, where deregulation of this process can lead to bone loss during ageing or osteoporosis. Keywords Mesenchymal stem/stromal cells . MSC . Epigenetics . Skeletal stem cells . DNA methylation . Histone methylation . Histone acetylation
Introduction The stromal component within bone marrow is a hierarchical continuum of mature functional stromal populations and committed progenitor cells. This is sustained by a minor population of long-lived, self-renewing and multipotential skeletal stem cells or bone marrow-derived mesenchymal stem/ stromal cells (BMSC) [1]. Purified preparation of human BMSC exhibit the potential to form osteoblasts, adipocytes, chondrocytes, smooth muscle cells and myelosupportive This article is part of the Topical Collection on Skeletal Biology and Regulation * Stan Gronthos [email protected] 1
Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
2
Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
fibroblasts under inductive conditions in vitro or when transplanted in vivo [2–4]. It is well known that the master regulatory transcription factors Runt-related transcription factor 2 (RUNX2), peroxisome proliferator-activated receptor gamma 2 (PPARγ2), myogenic differentiation (MOYD) and sex-determining region Y-box 9 (SOX9) are critical mediators of BMSC differentiation towards the osteogenic, adipogenic, myogenic and chondrogenic lineages, respectively [5–7]. The co-ordinated expressi
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