Inhibition of EZH2 Promotes Human Embryonic Stem Cell Differentiation into Mesoderm by Reducing H3K27me3

Yongxin Yu; Peng Deng; Bo Yu; John M. Szymanski; Tara Aghaloo; Christine Hong; Cun-Yu Wang

doi:10.1016/j.stemcr.2017.07.016

Stem Cell Reports (Sep 2017)

Inhibition of EZH2 Promotes Human Embryonic Stem Cell Differentiation into Mesoderm by Reducing H3K27me3

Yongxin Yu,
Peng Deng,
Bo Yu,
John M. Szymanski,
Tara Aghaloo,
Christine Hong,
Cun-Yu Wang

Affiliations

Yongxin Yu: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
Peng Deng: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
Bo Yu: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
John M. Szymanski: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
Tara Aghaloo: Section of Oral and Maxillofacial Surgery, Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
Christine Hong: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
Cun-Yu Wang: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA

DOI: https://doi.org/10.1016/j.stemcr.2017.07.016
Journal volume & issue: Vol. 9, no. 3
pp. 752 – 761

Abstract

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Mesoderm derived from human embryonic stem cells (hESCs) is a major source of the mesenchymal stem/stromal cells (MSCs) that can differentiate into osteoblasts and chondrocytes for tissue regeneration. While significant progress has been made in understanding of molecular mechanisms of hESC differentiation into mesodermal cells, little is known about epigenetic factors controlling hESC fate toward mesoderm and MSCs. Identifying potential epigenetic factors that control hESC differentiation will undoubtedly lead to advancements in regenerative medicine. Here, we conducted an epigenome-wide analysis of hESCs and MSCs and uncovered that EZH2 was enriched in hESCs and was downregulated significantly in MSCs. The specific EZH2 inhibitor GSK126 directed hESC differentiation toward mesoderm and generated more MSCs by reducing H3K27me3. Our results provide insights into epigenetic landscapes of hESCs and MSCs and suggest that inhibiting EZH2 promotes mesodermal differentiation of hESCs.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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