Identifying genes differentially expressed between PGCs and ES cells reveals a role for CREB-binding protein in genn cell survival
Identifying genes differentially expressed between PGCs and ES cells reveals a role for CREB-binding protein in genn cell survival
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DOI：
10.1016/j.ydbio.2007.08.029
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发表时间：
2007-11-15
影响因子：
2.7
通讯作者：
Donovan, Peter J.
中科院分区：
文献类型：
--
作者：
Elliott, Aaron M.;de Miguel, Maria P.;Donovan, Peter J.
原始生殖细胞（PGCs）是成年配子的胚胎前体。尽管在发育能力上受到限制，PGCs表达许多与多能胚胎干细胞（ES）相同的分子标记，并能在体内产生胚胎癌（EC）细胞，即睾丸肿瘤的干细胞。同样，当暴露于特定的生长因子时，PGCs可以在体外转化为多能胚胎胚（EG）细胞。在这里，我们提出在PGCs和ES细胞之间差异表达的基因是调节种系发育的良好候选者。为了确定调控生殖细胞发育和哺乳动物生殖能力的重要基因，我们对PGCs和ES细胞的全基因集进行了抑制减法杂交（SSH）。通过这种方法，我们发现与胚胎干细胞相比，转录辅助激活因子/组蛋白乙酰转移酶creb结合蛋白（CBP）在PGCs中高表达。为了阐明CBP在PGCs中的功能，我们制造了pgc特异性缺失CBP的小鼠。PGCs中CBP的缺失导致细胞凋亡增加，随后PGC数量减少。这些数据表明CBP在维持正常生殖细胞发育中起重要作用。(c) 2007爱思唯尔公司版权所有。
Primordial germ cells (PGCs) are the embryonic precursors of the adult gametes. Although restricted in developmental potency, PGCs express many of the same molecular markers as pluripotent embryonic stem (ES) cells and can give rise to embryonal carcinoma (EC) cells, the stem cells of testicular tumors, in vivo. Likewise, when exposed to specific growth factors in vitro PGCs can be converted into pluripotent embryonic germ (EG) cells. Here, we propose that genes differentially expressed between PGCs and ES cells are good candidates for regulating germline development. To identify genes important in regulating germ cell development and mammalian fertility, we performed suppression subtraction hybridization (SSH) between PGCs and ES cells whole gene set. Using this method, we identified the transcriptional coactivator/histone acetyltransferase CREB-binding protein (CBP) as being highly expressed in PGCs compared to ES cells. To elucidate the function of CBP in PGCs, we generated mice with a PGC-specific deletion of CBP. Loss of CBP in PGCs leads to increased apoptosis and subsequent reduction in PGC numbers. These data indicate an essential role for CBP in maintaining normal germ cell development. (c) 2007 Elsevier Inc. All rights reserved.