Gainey Daniel Patrick, Shubin Andrey V, Hunter Craig P
Department of Molecular and Cellular Biology, Harvard University, Divinity Avenue, The Biological Laboratory, Cambridge, United States.
Elife. 2025 Mar 26;13:RP100254. doi: 10.7554/eLife.100254.
We report our attempt to replicate reports of transgenerational epigenetic inheritance in . Multiple laboratories report that adults and their F1 embryos exposed to the pathogen show pathogen aversion behavior and increased reporter gene expression. However, results from one group show persistence of both through the F4 generation. We failed to consistently detect either the avoidance response or elevated expression beyond the F1 generation. We confirmed that the dsRNA transport proteins SID-1 and SID-2 are required for intergenerational (F1) inheritance of pathogen avoidance, but not for the F1 inheritance of elevated expression. Reanalysis of RNA seq data provides additional evidence that this intergenerational inherited PA14 response may be mediated by small RNAs. The experimental methods are well-described, the source materials are readily available, including samples from the reporting laboratory, and we explored a variety of environmental conditions likely to account for lab-to-lab variability. None of these adjustments altered our results. We conclude that this example of transgenerational inheritance lacks robustness, confirm that the intergenerational avoidance response, but not the elevated expression in F1 progeny, requires and , and identify candidate siRNAs and target genes that may mediate this intergenerational response.
我们报告了我们尝试在……中复制跨代表观遗传继承报告的情况。多个实验室报告称，暴露于病原体的成虫及其F1胚胎表现出病原体厌恶行为以及报告基因表达增加。然而，一组的结果显示这两者在F4代中持续存在。我们未能始终检测到F1代之后的回避反应或升高的……表达。我们证实，dsRNA转运蛋白SID-1和SID-2是病原体回避跨代（F1）遗传所必需的，但不是升高的……表达F1遗传所必需的。对RNA序列数据的重新分析提供了额外证据，表明这种跨代遗传的PA14反应可能由小RNA介导。实验方法描述详尽，源材料易于获取，包括来自报告实验室的样本，并且我们探索了各种可能解释实验室间差异的环境条件。这些调整均未改变我们的结果。我们得出结论，这种跨代遗传的例子缺乏稳健性，证实跨代回避反应（而非F1后代中升高的……表达）需要……和……，并鉴定了可能介导这种跨代反应的候选小干扰RNA和靶基因。
