Lysine-specific demethylase 1 inhibitors prevent teratoma development from human induced pluripotent stem cells.
Lysine-specific demethylase 1 inhibitors prevent teratoma development from human induced pluripotent stem cells.
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DOI：
10.18632/oncotarget.24030
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发表时间：
2018-01-19
期刊：
影响因子：
--
通讯作者：
Furukawa Y
中科院分区：
文献类型：
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作者：
Osada N;Kikuchi J;Umehara T;Sato S;Urabe M;Abe T;Hayashi N;Sugitani M;Hanazono Y;Furukawa Y
人类诱导多能干细胞（hiPSCs）为再生医学带来了巨大的期望。然而，必须制定安全策略，以防止hipsc来源的细胞移植到患者体内后形成畸胎瘤。近年来的研究表明，表观遗传调控因子在肿瘤发生的初始阶段起作用。使用功能获得和功能丧失的方法，我们在这里表明，赖氨酸特异性去甲基酶1 （LSD1）的表达和功能在hipsc中受到严格调控，其解除调控是畸胎瘤发展的基础。与这些结果一致，我们证明LSD1抑制剂S2157可以阻止hipsc移植到免疫缺陷小鼠体内形成畸胎瘤。LSD1的这种新作用及其抑制作用可能为利用hipsc开发新的临床应用和治疗策略提供了可能。
Human induced pluripotent stem cells (hiPSCs) are creating great expectations for regenerative medicine. However, safety strategies must be put in place to guard against teratoma formation after transplantation of hiPSC-derived cells into patients. Recent studies indicate that epigenetic regulators act at the initial step of tumorigenesis. Using gain-of-function and loss-of-function approaches, we show here that the expression and function of lysine-specific demethylase 1 (LSD1) are tightly regulated in hiPSCs, and their deregulation underlies the development of teratomas. Consistent with these results, we demonstrate that an LSD1 inhibitor, S2157, prevented teratoma formation from hiPSCs transplanted into immunodeficient mice. This novel action of LSD1 and the effects of its inhibition potentially allow for the development of new clinical applications and therapeutic strategies using hiPSCs.