Bereshchenko Oxana, Mancini Elena, Luciani Luisa, Gambardella Adriana, Riccardi Carlo, Nerlov Claus
EMBL Mouse Biology Unit, Monterotondo, Italy.
Haematologica. 2012 Sep;97(9):1291-4. doi: 10.3324/haematol.2011.060251. Epub 2012 Feb 27.
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.
Pontin是一种高度保守的DNA解旋酶/ATP酶，它是几种大分子复合物的组成部分，其功能包括DNA修复、端粒维持和肿瘤抑制。虽然已知Pontin在酵母、果蝇和青蛙中至关重要，但其在哺乳动物机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的基因Ruvbl1进行种系失活，我们发现它对早期胚胎发育至关重要，因为Ruvbl1基因敲除的胚胎在囊胚阶段之后无法存活，此时多能内细胞团的增殖受到损害。在造血组织中对Ruvbl1进行条件性消融导致骨髓衰竭。竞争性再增殖实验表明，这包括造血干细胞通过凋亡而丧失。因此，Pontin对胚胎多能细胞和成年造血干细胞的功能均至关重要。
