Pontin is essential for murine hematopoietic stem cell survival
Pontin is essential for murine hematopoietic stem cell survival
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DOI：
10.3324/haematol.2011.060251
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发表时间：
2012-09-01
期刊：
影响因子：
--
通讯作者：
Nerlov, Claus
中科院分区：
文献类型：
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作者：
Bereshchenko, Oxana;Mancini, Elena;Nerlov, Claus
Pontin是一种高度保守的DNA解旋酶/ATPase，它是几个大分子复合体的组成部分，具有DNA修复、端粒维持和肿瘤抑制等功能。虽然已知Pontin在酵母、果蝇和青蛙中是必不可少的，但它在哺乳动物生物体中的生理作用仍有待确定。我们在此发现，Pontin在胚胎干细胞和造血组织中高度表达。通过对编码Pontin的Ruvbl1基因进行种系失活，我们发现它对早期胚胎发育是必不可少的，因为Ruvbl1缺失的胚胎不能在囊胚期以后恢复，因为囊胚期多能内细胞团的增殖受到损害。有条件地去除造血组织中的Ruvbl1会导致骨髓衰竭。竞争性再繁殖实验表明，这包括通过细胞凋亡导致的造血干细胞的损失。因此，桥蛋白对胚胎多能细胞和成人造血干细胞的功能都是必不可少的。
Pontin is a highly conserved DNA helicase/ATPase which is a component of several macromolecular complexes with functions that include DNA repair, telomere maintenance and tumor suppression. While Pontin is known to be essential in yeast, fruit flies and frogs, its physiological role in mammalian organisms remains to be determined. We here find that Pontin is highly expressed in embryonic stem cells and hematopoietic tissues. Through germline inactivation of Ruvbl1, the gene encoding Pontin, we found it to be essential for early embryogenesis, as Ruvbl1 null embryos could not be recovered beyond the blastocyst stage where proliferation of the pluripotent inner cell mass was impaired. Conditional ablation of Ruvbl1 in hematopoietic tissues led to bone marrow failure. Competitive repopulation experiments showed that this included the loss of hematopoietic stem cells through apopotosis. Pontin is, therefore, essential for the function of both embryonic pluripotent cells and adult hematopoietic stem cells.