Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells
Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells
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DOI：
10.1038/ncomms4174
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发表时间：
2014-01
影响因子：
16.6
通讯作者：
Dongmei Zhu;Stefanie Hölz;E. Metzger;M. Pavlovic;A. Jandausch;C. Jilg;P. Galgóczy;Corinna Herz
中科院分区：
文献类型：
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作者：
Dongmei Zhu;Stefanie Hölz;E. Metzger;M. Pavlovic;A. Jandausch;C. Jilg;P. Galgóczy;Corinna Herz
干细胞群的增殖和分化受到严格调控，以提供足够的细胞数量用于组织形成，同时维持干细胞库。哺乳动物胎盘的胚胎部分由侵入母体蜕膜的分化的滋养层干细胞（TSCs）产生。在这里，我们证明，赖氨酸特异性脱甲基酶1（Lsd1）调节分化开始的TSCs。Lsd 1基因缺失可导致小鼠TSC数量减少、滋养外胚层组织形成减少和早期胚胎死亡，Lsd 1基因缺失的TSC表现出分化起始的特征，包括细胞形态改变、迁移和侵袭能力增强。我们发现，增加TSC运动介导的转录因子Ovol2的过早表达，直接抑制Lsd1在未分化的细胞。总之，我们的数据表明，表观遗传修饰剂Lsd 1的功能作为一个看门人的分化开始的TSC，从而分化相关的细胞迁移是由转录因子Ovol 2控制。
Propagation and differentiation of stem cell populations are tightly regulated to provide sufficient cell numbers for tissue formation while maintaining the stem cell pool. Embryonic parts of the mammalian placenta are generated from differentiating trophoblast stem cells (TSCs) invading the maternal decidua. Here we demonstrate that lysine-specific demethylase 1 (Lsd1) regulates differentiation onset of TSCs. Deletion ofLsd1in mice results in the reduction of TSC number, diminished formation of trophectoderm tissues and early embryonic lethality.Lsd1-deficient TSCs display features of differentiation initiation, including alterations of cell morphology, and increased migration and invasion. We show that increased TSC motility is mediated by the premature expression of the transcription factorOvol2that is directly repressed by Lsd1 in undifferentiated cells. In summary, our data demonstrate that the epigenetic modifier Lsd1 functions as a gatekeeper for the differentiation onset of TSCs, whereby differentiation-associated cell migration is controlled by the transcription factorOvol2.