孤舟蓑笠翁
(2025-06-27 20:21):
#paper 【doi】10.1126/science.adp0176；【发表年份】2025年；【期刊】Science；【标题】Reactivation of mammalian regeneration by turning on an evolutionarily disabled genetic switch。【内容总结】这篇论文研究了哺乳动物耳廓再生能力差异的遗传机制，目标是找到导致小鼠和大鼠失去再生能力的关键基因开关。研究人员通过比较再生能力强的兔子、山羊和非洲刺鼠与非再生的小鼠、大鼠，发现再生失败的原因是伤口诱导的成纤维细胞(WIFs)中醛脱氢酶基因Aldh1a2表达不足，该基因负责合成视黄酸(RA)。主要方法包括单细胞RNA测序、空间转录组分析和转基因小鼠实验。结果显示，通过激活Aldh1a2或外源补充RA可以恢复小鼠耳廓再生能力，进化过程中多个Aldh1a2调控元件的失活导致了再生失败。简单说就是找到了控制哺乳动物再生的"开关基因"，并通过基因操作成功重启了小鼠的再生能力。
Science,
2025-6-26.
DOI: 10.1126/science.adp0176
Reactivation of mammalian regeneration by turning on an evolutionarily disabled genetic switch
Abstract:
<br> Mammals display prominent diversity in the ability to regenerate damaged ear pinna, but the genetic changes underlying the failure of regeneration remain elusive. We performed comparative single-cell and spatial transcriptomic analyses of rabbits and mice recovering from pinna damage. Insufficient retinoic acid (RA) production, caused by the deficiency of rate-limiting enzyme Aldh1a2 and boosted RA degradation, was responsible for the failure of mouse pinna regeneration. Switching on<br> Aldh1a2</i><br> or RA supplementation reactivated regeneration. Evolutionary inactivation of multiple<br> Aldh1a2-linked</i><br> regulatory elements accounted for the deficient<br> Aldh1a2</i><br> expression upon injury in mice and rats. Furthermore, the activation of<br> Aldh1a2</i><br> by a single rabbit enhancer was sufficient to improve ear pinna regeneration in transgenic mice. Our study identified a genetic switch involved in the evolution of regeneration.<br>
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