2024年4月25日，来自美国德克萨斯大学吴军等研究人员合作在《细胞》杂志发表了标题为“Generation of rat forebrain tissues in mice.”的研究成果，在小鼠体内生成大鼠前脑组织。
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。
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。
Highlights
- C-CRISPR enables quick candidate gene screening aiding blastocyst complementation
- Mouse and rat ESCs can both complement Hesx1−/− forebrain agenesis in mice
- Reconstituted rat forebrains in mice exhibit normal structure and function
- Rat forebrains in mice develop at mouse rates with rat-specific gene expression
Summary
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 Hesx1 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.
文章来源：
Jia Huang, Bingbing He, Xiali Yang et al, Generation of rat forebrain tissues in mice.DOI: 10.1016/j.cell.2024.03.017，Cell：最新IF：66.85
