{"id":404,"title":"Multiplexed embryo profiling links cellular state to zygotic genome activation in single cells","title_zh":"多重胚胎原位成像将单细胞细胞状态与合子基因组激活联系起来","url":"https://pubmed.ncbi.nlm.nih.gov/42897187","doi":"10.1038/s41467-026-77784-7","pmid":"42897187","journal":"Nat Commun","kind":"paper","lang":"en","published_at":"2026-09-17T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Hess M","Wyss MF","Wu E","Schaniel GM","Lüthi J","Rebagliati C","Hannuschke D","Vastenhouw NL","Gilmour D","Shamipour S","Pelkmans L"],"primary_topic":"early-embryo","topics":[{"slug":"early-embryo","score":4.0,"hits":["zygotic genome activation"]},{"slug":"ai-compute","score":1.0,"hits":["computer vision"]},{"slug":"animal-models","score":0.8,"hits":["zebrafish"]}],"topic_score":4.0,"preference_score":10.0,"preference_labels":["卵母细胞-胚胎转换 / 母源-合子转换"],"llm_score":73.0,"final_score":91.0,"score_dims":{"novelty":86,"rigor":78,"impact":68,"relevance":58,"translation":42},"recommend_reason":"方法学上有实质突破：3D-4i 实现全胚胎多重蛋白状态高分辨定量，并首次系统把细胞周期时相与染色质/转录因子状态整合用于预测单细胞 ZGA 转录输出，对理解母源-合子转换机制有参考价值；但模型为斑马鱼，与人类 ART 临床的直接转化距离较远，属值得一读的方法学/机制类文献。","keywords":["三维迭代免疫荧光成像(3D-4i)","合子基因组激活","母源-合子转换","细胞周期时相","斑马鱼胚胎","单细胞空间多组学"],"selected":1,"story_id":438,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"nat-commun","journal_tier":"cns-sub","journal_if":14.7,"is_mock":false,"summary_zh":"该研究建立了高通量三维全胚胎迭代免疫荧光成像（3D-4i）与配套计算机视觉分析流程，可在数百个样本中从亚细胞到整胚胎尺度定量形态与分子特征。作者将其应用于经历中期囊胚转换的早期斑马鱼胚胎，逐细胞判定细胞周期时相，刻画了全局准同步有丝分裂波向细胞周期去同步化的时空动态；统计分析显示细胞周期时相是分裂周期内转录变异的主要来源，结合关键转录因子与染色质修饰状态可较准确预测单细胞在合子基因组激活期的转录输出。研究为多模态、多尺度解析多细胞自组织提供了新方法。","summary":"Multicellular self-organization depends on interactions across multiple length scales, yet mapping protein states at high spatial resolution in whole-mount embryos remains challenging. Here, we introduce high-throughput 3D in toto iterative immunofluorescence imaging (3D-4i) and a dedicated computer vision pipeline to quantify morphological and molecular features from subcellular to whole-embryo scales across hundreds of samples. Applying this pipeline to early zebrafish embryos undergoing mid-blastula transition, we determine the cell cycle phase for each cell across the embryo, and uncover the spatiotemporal dynamics by which global meta-synchronous mitotic waves transition to cell cycle desynchronization. Using statistical analysis, we find that the cell cycle phase is the major source of variability in transcription within a division cycle, and combining this with the analysis of key transcription factors and chromatin modifier state, included in our multiplexed dataset, enables accurate prediction of transcriptional output during zygotic genome activation in individual cells. Together, these findings establish 3D-4i as a powerful approach for quantifying multimodal, multiscale biological processes underlying multicellular self-organization.","interpretation_basis":null,"fulltext_status":"error","interpretation":null,"fulltext":{"available":false,"status":"error","reason":"抓取失败：HTTP 500 https://www.ebi.ac.uk/europepmc/webservices/rest/PMC13680386/fullTextXML","pmcid":"PMC13680386","license":null,"chars":0,"source":"Europe PMC","fetched_at":"2026-11-08T03:59:59+00:00"}}