分裂霉素，一种SIRT1抑制剂，可增强小鼠胚胎干细胞的造血分化。
Splitomicin, a SIRT1 Inhibitor, Enhances Hematopoietic Differentiation of Mouse Embryonic Stem Cells.
作者信息
Park Jeong-A, Park Sangkyu, Park Woo-Youn, Han Myung-Kwan, Lee Younghee
机构信息
Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju, Korea.
Biotechnology Research Institute, Chungbuk National University, Cheongju, Korea.
出版信息
Int J Stem Cells. 2019 Mar 30;12(1):21-30. doi: 10.15283/ijsc18040.
BACKGROUND AND OBJECTIVES
Embryonic stem (ES) cells have pluripotent ability to differentiate into multiple tissue lineages. SIRT1 is a class III histone deacetylase which modulates chromatin remodeling, gene silencing, cell survival, metabolism, and development. In this study, we examined the effects of SIRT1 inhibitors on the hematopoietic differentiation of mouse ES cells.
METHODS AND RESULTS
Treatment with the SIRT1 inhibitors, nicotinamide and splitomicin, during the hematopoietic differentiation of ES cells enhanced the production of hematopoietic progenitors and slightly up-regulated erythroid and myeloid specific gene expression. Furthermore, treatment with splitomicin increased the percentage of erythroid and myeloid lineage cells.
CONCLUSIONS
Application of the SIRT1 inhibitor splitomicin during ES cell differentiation to hematopoietic cells enhanced the yield of specific hematopoietic lineage cells from ES cells. This result suggests that SIRT1 is involved in the regulation of hematopoietic differentiation of specific lineages and that the modulation of the SIRT1 activity can be a strategy to enhance the efficiency of hematopoietic differentiation.
背景与目的
胚胎干细胞（ES细胞）具有分化为多种组织谱系的多能性。SIRT1是一种III类组蛋白去乙酰化酶，可调节染色质重塑、基因沉默、细胞存活、代谢及发育。在本研究中，我们检测了SIRT1抑制剂对小鼠ES细胞造血分化的影响。
方法与结果
在ES细胞造血分化过程中，用SIRT1抑制剂烟酰胺和裂霉素处理，可增强造血祖细胞的产生，并轻微上调红系和髓系特异性基因表达。此外，用裂霉素处理可增加红系和髓系谱系细胞的百分比。
结论
在ES细胞向造血细胞分化过程中应用SIRT1抑制剂裂霉素，可提高ES细胞中特定造血谱系细胞的产量。该结果表明，SIRT1参与特定谱系造血分化的调控，调节SIRT1活性可能是提高造血分化效率的一种策略。
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