Genetic Analysis of the Role of the Reprogramming Gene LIN-28 in Human Embryonic Stem Cells
Genetic Analysis of the Role of the Reprogramming Gene LIN-28 in Human Embryonic Stem Cells
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DOI：
10.1634/stemcells.2008-0720
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发表时间：
2009-01-01
期刊：
影响因子：
5.2
通讯作者：
Benvenisty, Nissim
中科院分区：
文献类型：
--
作者：
Darr, Henia;Benvenisty, Nissim
LIN - 28是一个近期被发现参与体细胞向诱导多能干细胞转化的基因。我们先前已表明LIN - 28在人类胚胎干细胞（HESCs）中高度表达；然而，其在这些细胞中的作用尚未被研究。我们现在表明，如同OCT4、SOX2和NANOG一样，LIN - 28在人类胚胎干细胞分化为拟胚体的过程中表达下调。此外，我们通过调控LIN - 28的表达水平来研究其在人类胚胎干细胞中的作用。LIN - 28的过表达会损害细胞在克隆密度下生长的能力，这是由于分化增加和细胞分裂减少所致。对这些条件下细胞分化的分析显示，其主要朝着胚外内胚层谱系分化。而且，我们表明，在小鼠早期发育过程中，在胚外内胚层中也观察到高水平的Lin - 28，因此似乎在体外和体内，高水平的LIN - 28都可能决定胚外内胚层的命运。然而，LIN - 28似乎对于人类胚胎干细胞的自我更新是可有可无的；其下调既不损害人类胚胎干细胞的增殖，也不会导致它们分化。因此，LIN - 28似乎不参与人类胚胎干细胞的自我更新，而是似乎参与它们从自我更新向分化转变的决策。《干细胞》2009年；27卷：352 - 362页
LIN-28 is a gene recently shown to be involved in the conversion of somatic cells to induced pluripotent stem cells. We have previously shown that LIN-28 is highly expressed in human embryonic stem cells (HESCs); however, its role in these cells has not been investigated. We now show that, like OCT4, SOX2, and NANOG, LIN-28 is downregulated during differentiation of HESCs into embryoid bodies. In addition, we investigate the role of LIN-28 in HESCs by manipulation of its expression levels. LIN-28 overexpression impairs the ability of cells to grow at clonal densities, due to increased differentiation and decreased cell division. Analysis of cell differentiation under these conditions revealed that it is mostly towards the extraembryonic endoderm lineage. Moreover, we show that, during early mouse development, high levels of Lin-28 are also observed in the extraembryonic endoderm, and therefore it seems that, both in vitro and in vivo, high levels of LIN-28 may specify an extraembryonic endoderm fate. However, LIN-28 seems dispensable for self-renewal of HESCs; its downregulation neither impairs HESC proliferation nor leads to their differentiation. Thus, LIN-28 does not seem to be involved in the self-renewal of HESCs, but rather seems to be involved in their decision to switch from self-renewal to differentiation. STEM CELLS 2009; 27: 352-362