Inhibition of EZH2 Promotes Human Embryonic Stem Cell Differentiation into Mesoderm by Reducing H3K27me3
Authors: Peng Deng
Christine Hong
Yongxin Yu
Tara Aghaloo
Cun-Yu Wang
Bo Yu
John M Szymanski
Journal: Stem cell reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EZH2; cell fate; epigenetics; histone methylation; human ESCs
Affiliations: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA., 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., Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ., Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Broad Stem Cell Research Institute and Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: .

Abstract:  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. 

Retracted: No

PubPeer comments:
 Microscope photos from different cell lines in Fig.S2A are the same, just rotated. # **Fig.S2A** ![file] , 
 #1 Thank you very much for altering this error. We immediately contacted the co-first authors. We were able to locate the raw images for the related experiments. As it turns out, the similar field of H1-vehicle cells was imaged twice, one of which was saved under the wrong folder by mistake. The first author mistakenly took the image from the wrong folder as she assembled the figure. We have contacted the Journal for corrections. , 
 December 2018 correction, which is hard to find at the original paper s website. Found here: https: www.cell.com action showPdf?pii=S2213-6711%2818%2930481-8 It reads: * In Figure S2A of our originally published Supplemental Information, the image labeled as the ALP staining of H9-vehicle (control) hESCs was incorrectly chosen. We imaged two similar fields of H1-vehicle cells, and one of these images was saved as an H9 image by mistake, resulting in a duplication. The correct image for H9-vehicle cells now appears below. In addition, the bar graph in Figure S3E was inadvertently omitted during file conversion in preparation for publication. The correct Figure S3E panel now appears below. We apologize for these oversights. The errors do not affect any of our original conclusions.* Thank you, authors, for correcting the figure and bar graph. ,