近日，美国德克萨斯大学吴军等研究人员合作在小鼠体内生成大鼠前脑组织。2024年4月25日，《细胞》杂志发表了这项成果。

研究人员开发了一种基于C-CRISPR的优化种间囊胚互补（IBC）策略，该策略有助于快速筛选候选基因，并确定Hesx1缺乏可支持通过IBC在小鼠体内生成大鼠前脑组织。成年小鼠的异种大鼠前脑组织在结构和功能上都是完整的。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，但却保持了类似大鼠的转录组特征。

随着发育的进行，大鼠细胞的嵌合率逐渐下降，这表明在出生前中后期的发育过程中存在异种障碍。种间前脑互补为研究大脑发育，和认知功能的演化保守机制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潜力。

据悉，IBC为研究发育提供了一个独特的平台，并有可能解决全球器官短缺的问题。尽管最近取得了成功，但脑组织尚未通过IBC实现。

附：英文原文

Title: Generation of rat forebrain tissues in mice

Author: Jia Huang, Bingbing He, Xiali Yang, Xin Long, Yinghui Wei, Leijie Li, Min Tang, Yanxia Gao, Yuan Fang, Wenqin Ying, Zikang Wang, Chao Li, Yingsi Zhou, Shuaishuai Li, Linyu Shi, Seungwon Choi, Haibo Zhou, Fan Guo, Hui Yang, Jun Wu

Issue&Volume: 2024/04/25

Abstract: Interspecies blastocyst complementation (IBC) provides a unique platform to studydevelopment and holds the potential to overcome worldwide organ shortages. Despiterecent successes, brain tissue has not been achieved through IBC. Here, we developedan optimized IBC strategy based on C-CRISPR, which facilitated rapid screening ofcandidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneicrat forebrain tissues in adult mice were structurally and functionally intact. Cross-speciescomparative analyses revealed that rat forebrain tissues developed at the same paceas the mouse host but maintained rat-like transcriptome profiles. The chimeric rateof rat cells gradually decreased as development progressed, suggesting xenogeneicbarriers during mid-to-late pre-natal development. Interspecies forebrain complementationopens the door for studying evolutionarily conserved and divergent mechanisms underlyingbrain development and cognitive function. The C-CRISPR-based IBC strategy holds greatpotential to broaden the study and application of interspecies organogenesis.

DOI: 10.1016/j.cell.2024.03.017

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00308-8