Esrrb Complementation Rescues Development of Nanog-Null Germ Cells.
Esrrb Complementation Rescues Development of Nanog-Null Germ Cells.
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ESRRB互补挽救了纳米无效生殖细胞的发展。
DOI：
10.1016/j.celrep.2017.12.060
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发表时间：
2018-01-09
期刊：
影响因子：
8.8
通讯作者：
Chambers I
中科院分区：
文献类型：
--
作者：
Zhang M;Leitch HG;Tang WWC;Festuccia N;Hall-Ponsele E;Nichols J;Surani MA;Smith A;Chambers I
转录因子Nanog和Esrrb在胚胎干细胞和原始生殖细胞的发育过程中起着重要作用。Esrrb是ESC中NANOG的正调控直接靶标，其可以定性地替代ESC中的Nanog功能。这种功能性取代是否延伸到生殖系尚不清楚。在这里，我们表明，种系缺失Nanog减少PGC数5倍，在妊娠中期。尽管这种定量消耗，与以前的发现相反，Nanog无效PGC可以完成种系发育。Nanog-null ESC的PGC样细胞（PGCLC）分化也受损，其中Nanog-null PGCLC显示出增殖降低和凋亡增加。然而，Esrrb的诱导表达与Nanog一样有效地恢复PGCLC数量。这些作用在体内重现：敲入Esrrb到Nanog使PGC数量恢复到野生型水平，并产生可生育的成年小鼠。这些发现表明Esrrb可以取代生殖细胞中的Nanog功能。Nanog的种系缺失减少了PGC数量，但没有消除PGC发育没有Nanog，PGCLC形成无效，增殖减少，凋亡增加Nanog靶基因Esrrb可以挽救Nanog−/− ESC的PGCLC分化Nanog基因座处Esrrb的敲入恢复了PGC发育效率尽管在幼稚多能细胞中有功能的转录因子也在原始生殖细胞（PGC）中表达，PGC的作用尚不清楚。在这里，Zhang et al.表明，在没有Nanog情况下，PGC不能有效地形成，但是通过诱导表达NANOG靶基因Esrrb可以恢复正常的PGC发育。
The transcription factors (TFs) Nanog and Esrrb play important roles in embryonic stem cells (ESCs) and during primordial germ-cell (PGC) development. Esrrb is a positively regulated direct target of NANOG in ESCs that can substitute qualitatively for Nanog function in ESCs. Whether this functional substitution extends to the germline is unknown. Here, we show that germline deletion of Nanog reduces PGC numbers 5-fold at midgestation. Despite this quantitative depletion, Nanog-null PGCs can complete germline development in contrast to previous findings. PGC-like cell (PGCLC) differentiation of Nanog-null ESCs is also impaired, with Nanog-null PGCLCs showing decreased proliferation and increased apoptosis. However, induced expression of Esrrb restores PGCLC numbers as efficiently as Nanog. These effects are recapitulated in vivo: knockin of Esrrb to Nanog restores PGC numbers to wild-type levels and results in fertile adult mice. These findings demonstrate that Esrrb can replace Nanog function in germ cells. Germline deletion of Nanog reduces PGC numbers but does not abolish PGC development Without Nanog, PGCLCs form ineffectively with less proliferation and more apoptosis The Nanog target gene Esrrb can rescue PGCLC differentiation of Nanog−/− ESCs Knockin of Esrrb at the Nanog locus restores PGC development efficiency Although transcription factors functional in naive pluripotent cells are also expressed in primordial germ cells (PGCs), their PGC role remains unclear. Here, Zhang et al. show that, without Nanog, PGCs form ineffectively but that normal PGC development can be restored by induced expression of the NANOG target gene Esrrb.
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DOI：
10.1126/science.1229277
发表时间：
2013-01-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hackett JA;Sengupta R;Zylicz JJ;Murakami K;Lee C;Down TA;Surani MA
通讯作者：
Surani MA
影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
DOI：
10.1242/dev.142679
发表时间：
2017-02-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Smith A
通讯作者：
Smith A
影响因子：
5.6
作者：
Mullin NP;Gagliardi A;Khoa LTP;Colby D;Hall-Ponsele E;Rowe AJ;Chambers I
通讯作者：
Chambers I
影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S