biostudies-literatureDeng PU.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial ResearchNIDCR NIH HHSNCI NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)39https://www.ebi.ac.uk/biostudies/studies/S-EPMC7672114biostudies-literatureUnknown8(1)Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs) have significant potential for cell-mediated bone regeneration. Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs. In this study, an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6 (GDF6), which is involved in bone formation, was the most upregulated gene associated with MSCs compared to hESCs. Furthermore, we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population. Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.Bone researchGrowth differentiation factor 6, a repressive target of EZH2, promotes the commitment of human embryonic stem cells to mesenchymal stem cells.PMC7672114R01DE016513P30 CA016042K08 DE024603Wang CYDeng PYu YHong CfalseGrowth differentiation factor 6, a repressive target of EZH2, promotes the commitment of human embryonic stem cells to mesenchymal stem cells.Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs) have significant potential for cell-mediated bone regeneration. Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs. In this study, an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6 (GDF6), which is involved in bone formation, was the most upregulated gene associated with MSCs compared to hESCs. Furthermore, we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population. Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.2020-01-01T00:00:00Z2020 Nov2024-10-19T13:01:13.98Z2021-02-20T10:54:58ZS-EPMC76721143329885710.1038/s41413-020-00116-y