{"id":351,"title":"Reconstructing the emergence of the human chorion via Hippo-mediated trophoblast induction","title_zh":"利用Hippo介导的滋养层诱导重建人绒毛膜发生","url":"https://pubmed.ncbi.nlm.nih.gov/42977768","doi":"10.1038/s41556-026-02082-9","pmid":"42977768","journal":"Nat Cell Biol","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Zhang M","Lim RL","Reis AH","Piszker W","Boyd WW","Pagon A","Mahajan A","Wu L","Zhao C","Petropoulos S","Ronda C","Simunovic M"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":6.0,"hits":["placenta","placental","trophoblast"]},{"slug":"early-embryo","score":1.0,"hits":["trophectoderm"]},{"slug":"omics-methods","score":1.0,"hits":["single-cell"]}],"topic_score":6.0,"preference_score":0.0,"preference_labels":[],"llm_score":88.0,"final_score":96.0,"score_dims":{"novelty":92,"rigor":88,"impact":88,"relevance":86,"translation":76},"recommend_reason":"该研究整合人滋养外胚层诱导、单细胞阶段匹配、DNA甲基化组与3D绒毛膜模型，为胎盘谱系指定和早期绒毛膜形成提供了可操作框架，对早期胚胎与胎盘研究有较高参考价值。","keywords":["滋养外胚层","人绒毛膜","Hippo-LATS-YAP","胎盘发育","三维模型","全基因组亚硫酸氢盐测序"],"selected":1,"story_id":131,"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":2,"has_interpretation":false,"journal_key":"nat-cell-biol","journal_tier":"cns-sub","journal_if":17.3,"is_mock":false,"summary_zh":"本研究以Hippo-LATS-YAP信号为切入点，建立无需外源形态发生素的人滋养外胚层诱导体系，并通过单细胞参考图谱进行阶段匹配，重建从早期滋养外胚层到次级绒毛膜谱系的发育轨迹。全基因组亚硫酸氢盐测序揭示先低甲基化后重甲基化及印记域等位偏好；悬浮聚集三维模型形成具极性及内外拓扑的人绒毛膜，并鉴定CLDN6+ITGA6-类EVT中间态。","summary":"Differential Hippo-LATS-YAP signalling controls the first mammalian cell-fate decision, yet how human trophectoderm specification progresses to chorion formation remains unknown. Here we establish a developmentally informed model in which LATS kinase inhibition initiates the trophectoderm trajectory without exogenous morphogens. Stage matching to an integrated embryo-chorion single-cell reference revealed ordered progression from early trophectoderm to secondary chorionic lineages. Whole-genome bisulfite sequencing showed a naive-like hypomethylated state followed by remethylation, with key known placenta-associated imprinted domains retaining methylation and allelic bias. We then established a three-dimensional human chorion model by agitating induced-cell aggregates in suspension, yielding secondary chorionic lineages that self-organized with outward-facing trophoblast polarity and inside-out stromal-epithelial topology. Endogenous WNT signalling was dispensable for initial trophectoderm induction but regulated later chorionic lineage balance. Isolating CLDN6+ITGA6- cells identified a proEVT-like intermediate with villous and extravillous potential. Together, this framework connects human trophectoderm induction to three-dimensional chorion modelling and enables investigation of placental specification.","interpretation_basis":null,"fulltext_status":"not_found","interpretation":null,"fulltext":{"available":false,"status":"not_found","reason":"Europe PMC 无此记录：DOI 10.1038/s41556-026-02082-9","pmcid":null,"license":null,"chars":0,"source":"Europe PMC","fetched_at":"2026-11-08T03:59:07+00:00"}}