Recently, interspecies chimera formation has been established in rodents by injection of rat pluripotent stem cells (PSCs) into mouse early embryos, and such a system provides an in vivo assay to test the developmental potential of human PSCs (hPSCs)1. In addition, the interspecies chimeras formed between hPSCs and large animal embryos would open new avenues to generate human tissues and organs for regenerative medicine2. In rodents, embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) have been derived from inner cell mass (ICM) of the blastocyst and post-implantation epiblast respectively3,4. Although both being pluripotent, the ESCs and EpiSCs are considered to represent two distinct states of pluripotency, the naïve and primed pluripotent state. Only naïve state ESCs can colonize the early embryos before the blastocyst stage to form adult chimeras and transmit to the germline, while the primed state EpiSCs can only integrate into the post-implantation embryos5,6. Intriguingly, although derived from the ICM, the human ESCs (hESCs) are similar to the mouse EpiSCs in many aspects such as the morphology and self-renewal pathways, hence they are considered to represent the primed pluripotent state. Several studies have reported the generation of human-animal interspecies chimeras using the stage-matching hESCs. For example, primed hPSCs were engrafted into in vitro cultured gastrula-stage mouse embryos to form chimeras, and the primed hPSCs were also converted into a naïve-like state and then were injected into pre-implantation embryos to form mouse or pig chimeras7,8,9.

中文翻译：

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人类胚胎干细胞在抑制细胞凋亡后有助于小鼠胚胎的胚胎和胚外谱系

最近，通过将大鼠多能干细胞（PSC）注射到小鼠早期胚胎中，在啮齿动物中建立了种间嵌合体形成，这种系统提供了一种体内测定法，以测试人PSC（hPSC）的发展潜力。此外，hPSC和大型动物胚胎之间形成的种间嵌合体将开辟新的途径，以产生用于再生医学的人体组织和器官2。在啮齿动物中，胚胎干细胞（ESCs）和表皮干细胞（EpiSCs）分别来自胚泡和植入后表皮细胞的内部细胞团（ICM）[3,4]。尽管ESC和EpiSC都是多能的，但它们被认为代表着两种不同的多能状态，即纯净的和准备好的多能状态。只有幼稚状态的胚胎干细胞才能在胚泡阶段之前定植早期的胚胎，以形成成年嵌合体并传播到种系，而初生状态的胚胎干细胞只能整合到植入后的胚胎中5,6。有趣的是，尽管人类ESC（hESC）源自ICM，但在形态学和自我更新途径等许多方面与小鼠EpiSC相似，因此被认为代表了启动的多能状态。几项研究报告了使用阶段匹配的hESCs产生人-动物种间嵌合体的过程。例如，将已灌注的hPSCs植入体外培养的胃胚期小鼠胚胎中形成嵌合体，然后将已灌注的hPSCs转化为幼稚状，然后注入植入前的胚胎中以形成小鼠或猪的嵌合体7,8。 ，9。