The germ cell determinant Blimp1 is not required for derivation of pluripotent stem cells.

The germ cell determinant Blimp1 is not required for derivation of pluripotent stem cells.
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DOI:
10.1016/j.stem.2012.02.023
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发表时间:
2012-07-06
期刊:
影响因子:
23.9
通讯作者:
Surani, M. Azim
Surani, M. Azim
中科院分区:
医学1区
文献类型:
--
作者:
Bao, Siqin;Leitch, Harry G.;Gillich, Astrid;Nichols, Jennifer;Tang, Fuchou;Kim, Shinseog;Lee, Caroline;Zwaka, Thomas;Li, Xihe;Surani, M. Azim

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Blimp1(Prdm1)是原始生殖细胞(PGC)的关键决定因子,与Prdm14在着床后上胚层细胞的PGC特化过程中起着组合作用。它们共同启动早期生殖细胞中的表观遗传重编程,使其成为潜在的多能状态,相当于胚胎干细胞(ESC)。虽然Prdm 14单独可以促进重编程,并且对多能状态的传播很重要,但尚不清楚Blimp 1是否也参与其中。通过使用遗传学方法,我们证明了Blimp1是胚胎干细胞和植入后外胚层干细胞(epiSCs)的衍生和维护的关键。值得注意的是,Blimp1也可以将epiSC重编程为ESC。因此,尽管Blimp1对于PGC特化是必需的,但它对于epiSC向ESC的回复以及此后的维持不是必需的。这项研究表明,重编程,包括体细胞的胚胎干细胞,可能不需要通过Blimp1阳性PGC样状态的强制性途径。Blimp1的敲除对ESC或epiSC的衍生或维持没有影响。Blimp1不是epiSC回复到ESC状态所必需的。Blimp1是PGC规范所必需的。证明了原始生殖细胞(PGCs)Blimp 1的关键决定因素是胚胎干细胞(ESC)和外胚层干细胞(epiSC)的衍生和重编程。这表明多能性的获得不需要通过Blimp1阳性PGC样状态的强制性途径。
Blimp1 (Prdm1), the key determinant of primordial germ cells (PGCs), plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells. They together initiate epigenetic reprogramming in early germ cells toward an underlying pluripotent state, which is equivalent to embryonic stem cells (ESCs). Whereas Prdm14 alone can promote reprogramming and is important for the propagation of the pluripotent state, it is not known whether Blimp1 is similarly involved. By using a genetic approach, we demonstrate that Blimp1 is dispensable for the derivation and maintenance of ESCs and postimplantation epiblast stem cells (epiSCs). Notably, Blimp1 is also dispensable for reprogramming epiSCs to ESCs. Thus, although Blimp1 is obligatory for PGC specification, it is not required for the reversion of epiSCs to ESCs and for their maintenance thereafter. This study suggests that reprogramming, including that of somatic cells to ESCs, may not entail an obligatory route through a Blimp1-positive PGC-like state. ► Knockout of Blimp1 has no effect on derivation or maintenance of ESCs or epiSCs ► Blimp1 is not required for reversion of epiSCs to an ESC state ► Blimp1 is required for PGC specification ► Transit through a PGC state is not obligatory for acquisition of pluripotency Bao et al. demonstrate that the key determinant of primordial germ cells (PGCs) Blimp1 is dispensable for the derivation of embryonic stem cells (ESCs) and epiblast stem cells (epiSCs) and for reprogramming. This suggests that acquisition of pluripotency does not entail an obligatory route through a Blimp1-positive PGC-like state.
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