Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.

中文翻译：

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小鼠前脑组织的生成

种间囊胚互补 (IBC) 提供了一个独特的发育研究平台，并具有克服全球器官短缺的潜力。尽管最近取得了一些成功，但脑组织尚未通过 IBC 获得。在这里，我们开发了一种基于 C-CRISPR 的优化 IBC 策略，该策略有助于快速筛选候选基因，并发现缺陷支持通过 IBC 在小鼠中生成大鼠前脑组织。成年小鼠的异种大鼠前脑组织结构和功能完整。跨物种比较分析表明，大鼠前脑组织的发育速度与小鼠宿主相同，但保持了与大鼠相似的转录组特征。大鼠细胞的嵌合率随着发育的进展逐渐降低，提示产前发育中后期存在异种障碍。种间前脑互补为研究大脑发育和认知功能背后的进化保守和差异机制打开了大门。基于C-CRISPR的IBC策略在拓宽种间器官发生的研究和应用方面具有巨大的潜力。