Principles of early human development and germ cell program from conserved model systems.
Principles of early human development and germ cell program from conserved model systems.
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DOI：
10.1038/nature22812
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发表时间：
2017-06-15
期刊：
影响因子：
64.8
通讯作者：
Surani MA
中科院分区：
文献类型：
--
作者：
Kobayashi T;Zhang H;Tang WWC;Irie N;Withey S;Klisch D;Sybirna A;Dietmann S;Contreras DA;Webb R;Allegrucci C;Alberio R;Surani MA
人类原始生殖细胞（human primordial germ cells，hPGCs）是精子和卵子的前体细胞，起源于胚胎着床后早期发育的第2-3周。使用hPGC诱导的体外模型，最近的研究表明人和小鼠PGC的特化存在显著的机制差异。这可能部分是由于其多能性网络的差异和早期植入后发育。由于早期人类胚胎无法进行直接研究，我们考虑了替代方案，包括猪胚胎，就像人类一样，发育为双层胚胎盘。在这里，我们表明，猪PGCs（pPGCs）起源于后部前原条主管外胚层的顺序上调SOX 17和BLIMP 1响应WNT和BMP信号。连同人类和猴子在体外模型模拟原肠胚形成期的发展，我们显示了保守的原则，外胚层发展的能力PGC的命运，其次是启动表观遗传程序，由一个平衡的SOX 17-BLIMP 1基因剂量调节。我们使用人、猪和猴的体内和体外模型的组合方法，提供了对早期人类发育的综合见解。
Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during week 2-3 of early postimplantation development. Using in vitro models of hPGC induction, recent studies suggest striking mechanistic differences in specification of human and mouse PGCs. This may partly be due to the divergence in their pluripotency networks, and early postimplantation development. Since early human embryos are inaccessible for direct studies, we considered alternatives, including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs (pPGCs) originate from the posterior pre-primitive streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. Together with human and monkey in vitro models simulating peri-gastrulation development, we show conserved principles for epiblast development for competency for PGC fate, followed by initiation of the epigenetic programme, regulated by a balanced SOX17–BLIMP1 gene dosage. Our combinatorial approach using human, porcine and monkey in vivo and in vitro models, provides synthetic insights on early human development.