The Germ Cell Fate of Cynomolgus Monkeys Is Specified in the Nascent Amnion

• Published in: Developmental cell 2016-10, Vol.39 (2), p.169-185
• Main Authors: Sasaki, Kotaro, Nakamura, Tomonori, Okamoto, Ikuhiro, Yabuta, Yukihiro, Iwatani, Chizuru, Tsuchiya, Hideaki, Seita, Yasunari, Nakamura, Shinichiro, Shiraki, Naoto, Takakuwa, Tetsuya, Yamamoto, Takuya, Saitou, Mitinori
• Format: Article
• Language: English
• Subjects: amnion; Amnion - cytology; Animals; Autocrine Communication - genetics; BLIMP1; BMP4; Cell Lineage; Cell Movement; cynomolgus monkeys (Macaca fascicularis); Embryo, Mammalian - cytology; epiblast; Fetus - cytology; Germ Cells - cytology; Germ Cells - metabolism; Gonads - cytology; Gonads - embryology; Humans; Macaca fascicularis; Mesoderm - metabolism; Models, Biological; monkeys; Pluripotent Stem Cells - cytology; primordial germ cells; Signal Transduction - genetics; SOX17; specification; Transcription Factors - metabolism; Transcription, Genetic; Transcriptome - genetics
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2016.09.007

The germ cell lineage ensures reproduction and heredity. The mechanism for germ cell specification in primates, including humans, has remained unknown. In primates, upon implantation the pluripotent epiblast segregates the amnion, an extra-embryonic membrane eventually ensheathing an embryo, and thereafter initiates gastrulation to generate three germ layers. Here, we show that in cynomolgus monkeys, the SOX17/TFAP2C/BLIMP1-positive primordial germ cells (cyPGCs) originate from the dorsal amnion at embryonic day 11 (E11) prior to gastrulation. cyPGCs appear to migrate down the amnion and, through proliferation and recruitment from the posterior amnion, expand in number around the posterior yolk sac by E17. Remarkably, the amnion itself expresses BMP4 and WNT3A, cytokines potentially critical for cyPGC specification, and responds primarily to them. Moreover, human PGC-like cells in vitro exhibit a transcriptome similar to cyPGCs just after specification. Our study identifies the origin of PGCs and a unique function of the nascent amnion in primates. [Display omitted] •A comprehensive analysis of PGC development in cynomolgus monkeys•cyPGCs originate in the nascent amnion prior to gastrulation of the epiblast•The amnion itself expresses and responds to signals for PGC specification•Human PGC-like cell transcriptome is similar to cyPGCs just after specification How primordial germ cells (PGCs) are specified in primate (including human) development is unknown. Sasaki et al. show that in cynomolgus monkeys, PGCs are specified in the early amnion, which may be an autocrine signaling center for specification. In-vitro-specified human PGCs exhibit a transcriptome similar to that of early monkey PGCs.