The role of Methyltransferase Ezh2 in Stem Cell growth and multi-differentiation — ASN Events
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The role of Methyltransferase Ezh2 in Stem Cell growth and multi-differentiation (#347)

Sarah E Hemming 1 2 3 , Dimitrios Cakouros 2 3 , Stan Gronthos 1 2 3
  1. Medicine, The University of Adelaide, Adelaide, SA, Australia
  2. Mesenchymal Stem Cell Group, Haematology, SA pathology, Adelaide, SA, Australia
  3. Centre for Stem Cell Research, Robinson Institute, Adelaide, SA, Australia

Bone marrow derived mesencymal stromal/stem cells  (MSCs) have the potential to differentiate and form osteoblasts, myoblasts, adipocytes, chondrocytes and myocytes under inductive conditions in vitro and when transplanted in vivo. However, the epigenetic changes during MSCs differentiation and the maintenace of the stem cell phenotype is not well understood. The methyltransferase Enhancer of Zeste homolog 2 (Ezh2) is known to repress gene expression through histone 3 lysine 27 tri-methylation (H3K27me3) modifications on chromatin. Previous studies have implicated Ezh2 in maintaining the stem cell phenotype of Haematopoietic Stem Cells (HSCs), Embryonic Stem Cells (ESCs) and multi-potent progenitor cells of the cerebral cortex in vitro12345. Furthermore, Cyclin Dependent Kinase 1 (CDK1) has been implicated as a regulator of Ezh2 in MSCs through an inhibitory phosphorylation on residue threonine (Thr) 487 on Ezh2 which promoted osteogenic differentiation 6. However, the direct role of Ezh2 on osteogenic and adipogenic differentiation and is still unclear. This study demonstrated that MSCs express known MSC surface antigen markers and can differentiate into adipocytes, osteoblasts and chondrocytes under differentiation conditions in vitro. Enforced expression of Ezh2 in MSCs enhanced the adipogenic and inhibited the osteogenic differentiation potential of MSCs in vitro. Conversely, inhibition of Ezh2 H3K27me3 activity by DZNep resulted in a decrease in adipogenic differentiation and an increase in osteogenic differentiation in MSCs in vitro. Furthermore, our study did not suggest that Ezh2 has a role in extending/increasing the life span of MSCs and proliferation potential of MSCs. However, further investigation into whether Ezh2 has a role in extending the life-span of MSCs. These findings implicate Ezh2 as a possible positive regulator of adipogenic differentiation and a negative regulator of osteogenic differentiation by MSCs in vitro.

  1. Bernstein B, Mikkelsen T, Xie X, Kamal M, Huebert D, Cuff J, Fry B, Meissner A, Wernig M, and Plath K. A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells. Cell 125: 315-326, 2006.
  2. De Haan G and Gerrits A. Epigenetic control of hematopoietic stem cell aging - The case of Ezh2. In: Hematopoietic Stem Cells.Oxford: Blackwell Publishing, 2007, p. 233-239.
  3. Kamminga LM, Bystrykh LV, Boer AC, Houwer S, Douma J, Weersing E, Dontje B, and de Haan G. The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 107: 2170-2179, 2006.
  4. Noer A, Boquest AC, and Collas P. Dynamics of adipogenic promoter DNA methylation during clonal culture of human adipose stem cells to senescence. BMC Cell Biol 8: 18, 2007.
  5. Pereira JD, Sansom SN, Smith J, Dobenecker MW, Tarakhovsky A, and Livesey FJ. Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex. Proceedings of the National Academy of Sciences 107: 15957-15962, 2010.
  6. Wei Y, Chen Y-H, Li L-Y, Lang J, Yeh S-P, Shi B, Yang C-C, Yang J-Y, Lin C-Y, Lai C-C, and Hung M-C. CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nature Cell Biology 13: 87-94, 2010.