Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, China.
Haihe Laboratory of Cell Ecosystem, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Cell Stem Cell. 2023 Apr 6;30(4):362-377.e7. doi: 10.1016/j.stem.2023.03.009.
Human stem cell-derived blastoids display similar morphology and cell lineages to normal blastocysts. However, the ability to investigate their developmental potential is limited. Here, we construct cynomolgus monkey blastoids resembling blastocysts in morphology and transcriptomics using naive ESCs. These blastoids develop to embryonic disk with the structures of yolk sac, chorionic cavity, amnion cavity, primitive streak, and connecting stalk along the rostral-caudal axis through prolonged in vitro culture (IVC). Primordial germ cells, gastrulating cells, visceral endoderm/yolk sac endoderm, three germ layers, and hemato-endothelial progenitors in IVC cynomolgus monkey blastoids were observed by single-cell transcriptomics or immunostaining. Moreover, transferring cynomolgus monkey blastoids to surrogates achieves pregnancies, as indicated by progesterone levels and presence of early gestation sacs. Our results reveal the capacity of in vitro gastrulation and in vivo early pregnancy of cynomolgus monkey blastoids, providing a useful system to dissect primate embryonic development without the same ethical concerns and access challenges in human embryo study.
人胚胎干细胞来源的拟胚体在形态和细胞谱系上与正常囊胚相似。然而，其发育潜能的研究能力有限。在这里，我们利用未分化的胚胎干细胞构建了类似于形态和转录组学的食蟹猴拟胚体。这些拟胚体通过延长体外培养（IVC），沿着头尾轴发育成具有卵黄囊、绒毛膜腔、羊膜腔、原条和连接柄结构的胚胎盘。通过单细胞转录组学或免疫染色观察到体外培养的食蟹猴拟胚体中的原始生殖细胞、原肠胚细胞、内脏内胚层/卵黄囊内胚层、三个胚层和造血内皮祖细胞。此外，将食蟹猴拟胚体移植到代孕体中可实现妊娠，这可通过孕激素水平和早期妊娠囊的存在来证实。我们的结果揭示了食蟹猴拟胚体体外原肠胚形成和体内早期妊娠的能力，为在不涉及人类胚胎研究的相同伦理问题和获取挑战的情况下，解析灵长类动物胚胎发育提供了一个有用的系统。
