Association of telomere length with authentic pluripotency of ES/iPS cells
Association of telomere length with authentic pluripotency of ES/iPS cells
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端粒长度与 ES/iPS 细胞真实多能性的关联
DOI：
10.1038/cr.2011.16
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发表时间：
2011-05-01
期刊：
影响因子：
44.1
通讯作者：
Liu, Lin
中科院分区：
文献类型：
--
作者：
Huang, Junjiu;Wang, Fang;Liu, Lin
端粒酶和端粒对干细胞的无限复制非常重要。最近，体细胞的端粒被发现在诱导多能干细胞（iPSC）中被重编程以伸长。然而，端粒在胚胎干细胞（ESC）或iPSC的体内发育多能性中的作用尚未直接解决。我们发现，具有长端粒的ESC表现出真实的发育多能性，这一点可以通过生成完整的ESC幼仔以及生殖系能力嵌合体来证明，这是啮齿动物中最严格的测试。具有短端粒的ESC显示减少的畸胎瘤形成和嵌合体产生，并且不能产生完整的ESC幼仔。端粒长度与胚胎干细胞的发育多能性高度相关（r > 0.8）。短端粒降低了ESC的增殖速率或能力，改变了与端粒表观遗传学相关的基因的表达，下调了对胚胎发生重要的基因，并破坏了生殖细胞分化。此外，具有较长端粒的iPSC产生嵌合体的效率高于具有短端粒的iPSC。我们的数据表明，功能性端粒是胚胎干细胞/诱导多能干细胞的发育多能性所必需的，并表明端粒长度可能提供一个有价值的标记，以评估干细胞多能性，特别是当严格的测试是不可行的。
Telomerase and telomeres are important for indefinite replication of stem cells. Recently, telomeres of somatic cells were found to be reprogrammed to elongate in induced pluripotent stem cells (iPSCs). The role of telomeres in developmental pluripotency in vivo of embryonic stem cells (ESCs) or iPSCs, however, has not been directly addressed. We show that ESCs with long telomeres exhibit authentic developmental pluripotency, as evidenced by generation of complete ESC pups as well as germline-competent chimeras, the most stringent tests available in rodents. ESCs with short telomeres show reduced teratoma formation and chimera production, and fail to generate complete ESC pups. Telomere lengths are highly correlated (r > 0.8) with the developmental pluripotency of ESCs. Short telomeres decrease the proliferative rate or capacity of ESCs, alter the expression of genes related to telomere epigenetics, down-regulate genes important for embryogenesis and disrupt germ cell differentiation. Moreover, iPSCs with longer telomeres generate chimeras with higher efficiency than those with short telomeres. Our data show that functional telomeres are essential for the developmental pluripotency of ESCs/iPSCs and suggest that telomere length may provide a valuable marker to evaluate stem cell pluripotency, particularly when the stringent tests are not feasible.