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Inhibition of BET selectively eliminates undifferentiated pluripotent stem cells

Science Bulletin 2018年第8期63卷 477-487页

作者： Jung Hyun Im Seon In Hwang Jong-Wan Kim soon-Jung Park Kyu-ree Kang jueng soo you Kee Pyo Kim Sung-Hwan Moon Hyuk-Jin Cha Hyung-Min Chung Hans R. Scholer Jung Keun Hyun DongWook Han Department of Stem Cell Biology School of Medicine Konkuk University Seoul 05029 Republic of Korea Department of Nanobiomedical Science Dankook University Graduate School Cheonan 330714 Republic of Korea Department of Biochemistry School of Medicine Konkuk University Seoul 05029 Republic of Korea Department of Cell and Developmental Biology Max Planck Institute for Molecular Biomedicine 48149 Munster Germany Department of Life Sciences College of Natural Sciences Sogang University Seoul 04107 Republic of Korea KU Open-lnnovation Center. Institute of Biomedical Science & Technology Konkuk University Seoul 05029 Republic of Korea Department of Advanced Translational Medicine School of Medicine Konkuk University Seoul 05029 Republic of Korea

Embryonic stem cells(ESCs) maintain their cellular identity through the systematic regulation of master transcription factors and chromatin remodeling complexes. Recent work has shown that the unusually large-scale enhancers—namely super-enhancers(SEs), on which BRD4, a member of the bromodomain and extraterminal domain(BET) family is highly enriched—could regulate pluripotency-related transcription factors. Moreover, inhibition of BRD4 binding on SEs has been shown to induce the differentiation of ESCs. However, the underlying mechanism of BRD4 inhibition-mediated stem cell differentiation remains elusive. Here we show that both mouse and human ESCs lose their capacity for self-renewal upon treatment with JQ1, a selective inhibitor of BET family including BRD4, with rapid suppression of pluripotency-associated genes. Notably, a high concentration of JQ1 could selectively eliminate ESCs via apoptosis, without affecting the functionality of differentiated somatic cells from ESCs, suggesting that inhibition of BET may have a beneficial effect on the development of pluripotent stem cell-based cell therapy.

关键词：干细胞 apoptosis 细胞治疗字符建筑群染色质约束力证明

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