GASZ promotes germ cell derivation from embryonic stem cells.
GASZ promotes germ cell derivation from embryonic stem cells.
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DOI：
10.1016/j.scr.2013.05.012
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发表时间：
2013-09
影响因子：
1.2
通讯作者：
Qian Wang;Xiqiang Liu;Nannan Tang;D. Archambeault;Jin Li;Huili Song;Chao Tang;B. He;M. Matz
中科院分区：
文献类型：
--
作者：
Qian Wang;Xiqiang Liu;Nannan Tang;D. Archambeault;Jin Li;Huili Song;Chao Tang;B. He;M. Matz
原始生殖细胞（PGCs）是发育中的胚胎的近外胚层形成的第一个生殖系群体。尽管它们具有重要的生物学意义，但在胚胎发育过程中，PGCs产生、迁移和分化为配子的调控网络仍然难以捉摸，这主要是由于早期胚胎中生殖细胞的数量有限。为了阐明控制早期生殖细胞发育的分子机制，我们利用胚胎干细胞（ESCs）的体外分化模型，筛选了一系列在成人生殖器官中特异性表达的候选基因。我们发现gasz的功能增加，一个先前报道参与出生后精母细胞减数分裂的基因，导致人类和小鼠ESCs中PGC形成最强烈的上调。相反，Gaszdeficiency导致ESC分化过程中生殖细胞明显减少，在胚胎早期发育过程中生殖嵴中MVH和DAZL的表达减少。进一步的分析表明，GASZ与一种关键的生殖细胞调节因子DAZL相互作用，协同促进胚胎干细胞的生殖细胞衍生。因此，我们的数据揭示了GASZ在胚胎生殖细胞发育中的潜在作用，并为胚胎发生过程中早期生殖细胞形成的分子途径提供了一个强大的体外系统。
Primordial germ cells (PGCs) are the first germ-line population that forms from the proximal epiblast of the developing embryo. Despite their biological importance, the regulatory networks whereby PGCs arise, migrate, and differentiate into gametes during embryonic development remains elusive, largely due to the limited number of germ cells in the early embryo. To elucidate the molecular mechanisms that govern early germ cell development, we utilized an in vitro differentiation model of embryonic stem cells (ESCs) and screened a series of candidate genes with specific expression in the adult reproductive organs. We discovered that gain of function ofGasz, a gene previously reported to participate in meiosis of postnatal spermatocytes, led to the most robust upregulation of PGC formation from both human and murine ESCs. In contrast,Gaszdeficiency resulted in pronounced reduction of germ cells during ESC differentiation and decreased expression of MVH and DAZL in genital ridges during early embryonic development. Further analyses demonstrated that GASZ interacted with DAZL, a key germ cell regulator, to synergistically promote germ cell derivation from ESCs. Thus, our data reveal a potential role of GASZ during embryonic germ cell development and provide a powerful in vitro system for dissecting the molecular pathways in early germ cell formation during embryogenesis.