{"id":354,"title":"Epiblast complementation enables generation of live offspring from pluripotent stem cells","title_zh":"上胚层互补：多能干细胞可完全替代宿主上胚层并产生存活子代","url":"https://pubmed.ncbi.nlm.nih.gov/42976859","doi":"10.1016/j.stem.2026.10.010","pmid":"42976859","journal":"Cell Stem Cell","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Ding Y","Oura S","Okamura D","Wu J"],"primary_topic":"early-embryo","topics":[{"slug":"early-embryo","score":5.0,"hits":["blastocyst","epiblast"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":83.0,"final_score":91.0,"score_dims":{"novelty":90,"rigor":85,"impact":82,"relevance":72,"translation":62},"recommend_reason":"将囊胚互补从“单器官”拓展至“整个上胚层”，并用单细胞水平的重建实验给出强证据，既提供了PSC发育潜能的功能性评定方法，也为ivG与基因修饰动物制备提供新范式；但属小鼠基础研究，距ART临床尚远。","keywords":["上胚层互补","多能干细胞","naive PSC","囊胚互补","发育潜能","小鼠遗传修饰"],"selected":1,"story_id":128,"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":3,"has_interpretation":false,"journal_key":"cell-stem-cell","journal_tier":"cns-sub","journal_if":19.8,"is_mock":false,"summary_zh":"该研究在小鼠中建立“上胚层互补”策略：通过人为制造宿主上胚层的发育空位，使供体多能干细胞（PSC）能够定植并替代宿主上胚层。结果显示，野生型与基因修饰的naive PSC均可完全替代宿主上胚层、贡献全部上胚层来源组织并产生存活子代；formative PSC同样能重建上胚层并支持发育至足月，提示其发育潜能与naive PSC相当。值得注意的是，单个naive PSC即足以重建上胚层并获得活体子代。作者据此提出，上胚层互补可作为评估PSC发育潜能的功能性实验，并为直接由培养PSC生成遗传背景明确的动物提供途径。","summary":"Blastocyst complementation enables the generation of donor pluripotent stem cell (PSC)-derived tissues in vivo, but its application has largely been limited to individual organs. Here, we establish epiblast complementation, a robust strategy for generating mice from donor PSCs. By creating an empty developmental niche in the host epiblast, we show that both wild-type and genetically modified naive PSCs can fully replace the host epiblast, contribute to all epiblast-derived tissues, and generate live offspring. Formative PSCs can also fully reconstitute the epiblast and support development to term, demonstrating developmental potential comparable to that of naive PSCs. Notably, a single naive PSC is sufficient to reconstitute the epiblast and give rise to live offspring. Together, these findings establish epiblast complementation as a functional assay for assessing PSC developmental potential and provide a strategy for generating genetically defined animals directly from cultured PSCs.","interpretation_basis":null,"fulltext_status":"not_found","interpretation":null,"fulltext":{"available":false,"status":"not_found","reason":"Europe PMC 无此记录：DOI 10.1016/j.stem.2026.10.010","pmcid":null,"license":null,"chars":0,"source":"Europe PMC","fetched_at":"2026-11-08T04:00:00+00:00"}}