{"id":490,"title":"Early Wnt inhibition promotes GnRH neuron differentiation by upregulating FGF8-FGFR1 signaling","title_zh":"早期Wnt抑制通过上调FGF8-FGFR1信号促进人GnRH神经元分化","url":"https://doi.org/10.1186/s12958-026-01635-9","doi":"10.1186/s12958-026-01635-9","pmid":null,"journal":"Reproductive Biology and Endocrinology","kind":"paper","lang":"en","published_at":"2026-11-06T00:00:00+00:00","fetched_at":"2026-11-08T03:44:35+00:00","authors":["Celia Gomez-Sanchez","Nazli Eskici","Shrinidhi Madhusudan","Kirsi Vaaralahti","Karoliina Tanner","Kristiina Pulli","Timo Tuuri","Yafei Wang","Taneli Raivio"],"primary_topic":"art-clinical","topics":[{"slug":"art-clinical","score":5.0,"hits":["gnrh","gonadotropin"]},{"slug":"omics-methods","score":1.0,"hits":["transcriptomic"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":78.0,"final_score":78.0,"score_dims":{"novelty":80,"rigor":78,"impact":68,"relevance":62,"translation":60},"recommend_reason":"首次在人源hPSC模型中解析Wnt抑制与FGF8-FGFR1的时序性交互在GnRH神经元发生中的作用，机制新颖、时序可控敲低设计扎实；但属发育机制研究，距ART临床与实验室决策较远，适合关注生殖内分泌与干细胞分化方向者阅读。","keywords":["GnRH神经元","Wnt抑制","FGF8-FGFR1","人多能干细胞","下丘脑-垂体-性腺轴","AID时序敲低"],"selected":1,"story_id":16,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"crossref-core-journals","source_name":"Crossref · 核心期刊新上线","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"rbe","journal_tier":"standard","journal_if":4.2,"is_mock":false,"summary_zh":"研究以人多能干细胞（hPSC）经Wnt与双SMAD抑制10天诱导GnRH神经元分化，并用生长素诱导降解子（AID）系统在10–20天时间窗内可控敲低FGFR1，结合FGF8b刺激与FGF8阻断及NPC与GnRH神经元的bulk RNA测序。结果显示，早期Wnt抑制无需外源FGF8b即可诱导GnRH神经元形成，可能通过上调前脑标志物与内源性FGF8实现；阻断内源FGF8或敲低FGFR1均削弱GnRH十肽分泌与GNRH1表达，而FGF8b可挽救GNRH1表达。结论：早期Wnt抑制经FGFR1介导的FGF8信号促进人GnRH神经元发育。","summary":"Abstract Background The FGF and Wnt pathways have been implicated in gonadotropin-releasing hormone (GnRH) deficiency, but their crosstalk during human GnRH neuron ontogeny remains unexplored. Methods GnRH neurons were differentiated from human pluripotent stem cells (hPSCs) by combining Wnt and dual SMAD inhibition for 10 days, followed by temporally-controlled FGFR1 depletion for 10–20 days using an auxin-inducible degron system. FGF8b stimulation and FGF8 blocking were tested. Transcriptomic changes in neural progenitor cells (NPCs) and GnRH neurons were examined using bulk RNA-sequencing. Results Early Wnt inhibition induced GnRH neuron formation without exogenous FGF8b, possibly by upregulating anterior forebrain markers and endogenous FGF8 in NPCs. Blocking this endogenous FGF8 diminished GnRH neuron formation. FGFR1 depletion in NPCs suppressed FGF8 expression, and neuron GnRH decapeptide secretion and GNRH1 expression. GNRH1 expression was rescued by FGF8b treatment. Conclusions Early Wnt inhibition promotes human GnRH neuron development through FGFR1-mediated FGF8 signaling. These findings advance the understanding of the complexity of FGF8-FGFR1 pathway interactions and their role in olfactory and hypothalamic neuron differentiation, particularly in GnRH neuron ontogeny.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}