2024年4月25日，來自美國德克薩斯大學吳軍等研究人員合作在《細胞》雜志發表了標題為“Generation of rat forebrain tissues in mice.”的研究成果，在小鼠體內生成大鼠前腦組織。
據悉，IBC為研究發育提供了一個獨特的平臺，并有可能解決全球器官短缺的問題。盡管最近取得了成功，但腦組織尚未通過IBC實現。
研究人員開發了一種基于C-CRISPR的優化種間囊胚互補（IBC）策略，該策略有助于快速篩選候選基因，并確定Hesx1缺乏可支持通過IBC在小鼠體內生成大鼠前腦組織。成年小鼠的異種大鼠前腦組織在結構和功能上都是完整的?？缥锓N比較分析表明，大鼠前腦組織的發育速度與小鼠宿主相同，但卻保持了類似大鼠的轉錄組特征。
隨著發育的進行，大鼠細胞的嵌合率逐漸下降，這表明在出生前中后期的發育過程中存在異種障礙。種間前腦互補為研究大腦發育，和認知功能的演化保守機制和差異機制打開了大門?；贑-CRISPR的IBC策略，在拓寬種間器官發生的研究和應用方面具有巨大潛力。
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.
文章來源：
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
