Human Genetics Graduate Program, UCLA, Los Angeles, CA 90095, USA.
Molecular Toxicology Inter-Departmental Program, UCLA, Los Angeles, CA 90095, USA.
Cell Rep. 2023 Jun 27;42(6):112535. doi: 10.1016/j.celrep.2023.112535. Epub 2023 May 23.
Single-cell transcriptomic platforms provide an opportunity to map an organism's response to environmental cues with high resolution. Here, we applied single-nucleus RNA sequencing (snRNA-seq) to establish the tissue and cell type-resolved transcriptome of the adult C. elegans and characterize the inter- and trans-generational transcriptional impact of ethanol. We profiled the transcriptome of 41,749 nuclei resolving into 31 clusters, representing a diverse array of adult cell types including syncytial tissues. Following exposure to human-relevant doses of alcohol, several germline, striated muscle, and neuronal clusters were identified as being the most transcriptionally impacted at the F1 and F3 generations. The effect on germline clusters was confirmed by phenotypic enrichment analysis as well as by functional validation, which revealed a remarkable inter- and trans-generational increase in germline apoptosis, aneuploidy, and embryonic lethality. Together, snRNA-seq represents a valuable approach for the detailed examination of an adult organism's response to environmental exposures.
单细胞转录组学平台提供了一个机会，可以高分辨率地绘制生物体对环境线索的反应图谱。在这里，我们应用单核 RNA 测序 (snRNA-seq) 来建立成年秀丽隐杆线虫的组织和细胞类型分辨转录组，并描述乙醇的跨代和代际转录影响。我们对 41749 个核进行了转录组分析，将其分为 31 个聚类，代表了包括合胞组织在内的各种成年细胞类型。在暴露于人类相关剂量的酒精后，几个生殖系、横纹肌和神经元簇在 F1 和 F3 代中被鉴定为转录受影响最大的簇。通过表型富集分析和功能验证证实了对生殖系簇的影响，该验证揭示了生殖系细胞凋亡、非整倍体和胚胎致死率的显著跨代和代际增加。总的来说，snRNA-seq 代表了一种对成年生物体对环境暴露反应进行详细研究的有价值的方法。
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