{"id":373,"title":"A CD4-lineage erythro-myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation","title_zh":"成人骨髓中发现CD4谱系红系-髓系祖细胞，构成巨噬细胞生成的替代途径","url":"https://pubmed.ncbi.nlm.nih.gov/42934292","doi":"10.1038/s41590-026-02686-1","pmid":"42934292","journal":"Nat Immunol","kind":"paper","lang":"en","published_at":"2026-10-26T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Tikoo S","Jain R","Martinez B","Song R","Wielscher M","Márquez-Burgoa C","Hladik A","Rizzetto S","Shaw LE","Ghannadan M","Gerhofer SA","Mitchell AJ","Torres-Pacheco ME","Luciani F","Farlik M","Wong JJL","Knapp S","Starkl P","Fraser ST","Jung S","Weninger W"],"primary_topic":"repro-immunology","topics":[{"slug":"repro-immunology","score":4.0,"hits":["macrophage"]},{"slug":"omics-methods","score":2.0,"hits":["single-cell rna","transcriptomic"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":63.0,"final_score":71.0,"score_dims":{"novelty":86,"rigor":85,"impact":55,"relevance":35,"translation":35},"recommend_reason":"发现成人骨髓中存在不依赖单核细胞的巨噬细胞生成替代途径，机制新颖且多组学验证较充分；但研究核心为造血/免疫学，与生殖医学和ART的直接关联有限，适合关注生殖免疫与胚胎来源巨噬细胞的研究者浏览。","keywords":["CD4谱系","红系-髓系祖细胞","巨噬细胞生成","成人骨髓","单细胞RNA测序","CCR2非依赖"],"selected":1,"story_id":321,"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-immunol","journal_tier":"cns-sub","journal_if":27.7,"is_mock":false,"summary_zh":"该研究在成人骨髓中鉴定出一群此前未被认识的CD4谱系红系-髓系祖细胞（EMPROR）。这类细胞在表型和转录组上不同于造血干细胞、共同髓系祖细胞及单核前体，不表达Csf1r和Ccr2而表达Cd4与Kit。结合单细胞RNA测序、RNA速度分析和谱系实验，研究显示其具有巨噬细胞、中性粒细胞、巨核细胞和红系分化潜能，可在不依赖CCR2介导单核细胞募集的情况下生成血管周和肿瘤相关巨噬细胞，并在炎症和肿瘤状态下贡献红系与粒系。转录组比较提示EMPROR最接近胚胎红系-髓系祖细胞，表明成人骨髓保留了类胚胎造血程序。","summary":"Tissue-resident macrophages originate from distinct developmental sources, but their adult replenishment is thought to depend exclusively on circulating monocytes. Here we identify a previously unrecognized CD4-lineage erythro-myeloid progenitor (EMPROR) in the adult bone marrow that provides an alternative pathway for macrophage generation. EMPROR cells are phenotypically and transcriptionally distinct from hematopoietic stem cells, common myeloid progenitors and monocyte precursors, lacking Csf1r and Ccr2 while expressing Cd4 and Kit. Single-cell RNA sequencing, RNA velocity analysis and lineage assays reveal macrophage, neutrophil, megakaryocytic and erythroid potential. EMPROR cells generate perivascular and tumor-associated macrophages independently of CCR2-mediated monocyte recruitment and contribute to erythroid and granulocytic lineages under inflammatory and neoplastic conditions. Transcriptomic comparisons position EMPROR cells closest to embryonic erythro-myeloid progenitors, indicating the persistence of an embryonic-like program in adult bone marrow. These findings reveal an alternative pathway of adult myelopoiesis that sustains macrophage diversity beyond the classical monocyte lineage.","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}}