Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development.

Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development.
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DOI:
10.1242/dev.083279
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发表时间:
2012-12
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Behr R
Behr R
中科院分区:
其他
文献类型:
--
作者:
Vogt EJ;Meglicki M;Hartung KI;Borsuk E;Behr R

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母体核仁是胚胎基因组(EGA)和早期胚胎发育的适当激活所必需的。核仁发生的特征是在植入前发育过程中由核仁前体(NPB)转化为成熟核仁。然而,NPBs的功能和参与的分子因子是未知的。我们发现了多能性因子LIN 28的新作用,其生物学意义先前在将人类体细胞重编程为诱导多能干细胞(iPS)中得到证实。在这里,我们发现LIN 28在NPB和小鼠植入前胚胎和胚胎干细胞(ESCs)的成熟核仁中积累,在那里它与核仁标记物B23(nucleophosmin 1)共定位。LIN 28在非人灵长类(NHP)植入前胚胎中具有核仁定位,但在NHP ESC中位于细胞质中。在小鼠EGA之前,LIN 28转录物显示出显著下降,而LIN 28蛋白在EGA时定位于NPB。在用Lin 28吗啉代敲低后,大多数胚胎停滞在2-和4-细胞阶段之间,并且从未发育成桑椹胚或胚泡。Lin 28注射吗啉的胚胎在2细胞期被阻滞,在假定的NPB位点没有富集核磷蛋白,表明功能性NPB没有组装。基于这些结果,我们提出LIN 28是早期胚胎发育过程中核发生的一个重要因子。
The maternal nucleolus is required for proper activation of the embryonic genome (EGA) and early embryonic development. Nucleologenesis is characterized by the transformation of a nucleolar precursor body (NPB) to a mature nucleolus during preimplantation development. However, the function of NPBs and the involved molecular factors are unknown. We uncover a novel role for the pluripotency factor LIN28, the biological significance of which was previously demonstrated in the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells. Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28 protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28 morpholino, the majority of embryos arrest between the 2- and 4-cell stages and never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB sites, indicating that functional NPBs were not assembled. Based on these results, we propose that LIN28 is an essential factor of nucleologenesis during early embryonic development.
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