{"id":371,"title":"Single-cell multi-omics reveals archetypal regulatory programs shared across T cell subsets","title_zh":"单细胞多组学揭示 T 细胞亚群间共享的“原型”调控程序","url":"https://pubmed.ncbi.nlm.nih.gov/42945216","doi":"10.1016/j.celrep.2026.118156","pmid":"42945216","journal":"Cell Rep","kind":"paper","lang":"en","published_at":"2026-10-26T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Walker SK","van der Veeken J","Rudensky AY","Pritykin Y"],"primary_topic":"ethics-policy","topics":[{"slug":"omics-methods","score":9.0,"hits":["epigenomic","multi-omics","rna-seq","single-cell"]},{"slug":"ethics-policy","score":4.0,"hits":["regulatory"]},{"slug":"oocyte","score":1.0,"hits":["follicular"]},{"slug":"repro-genetics","score":1.0,"hits":["atac-seq"]},{"slug":"repro-immunology","score":1.0,"hits":["immunotherapy"]}],"topic_score":9.0,"preference_score":10.0,"preference_labels":["多组学整合分析（任意生殖对象）"],"llm_score":44.0,"final_score":62.0,"score_dims":{"novelty":78,"rigor":76,"impact":40,"relevance":12,"translation":15},"recommend_reason":"这是一项高质量的免疫学单细胞多组学研究，方法学（多组学整合与调控模块识别）对胚胎多组学分析有间接借鉴意义；但研究对象是病毒感染中的 T 细胞，与生殖医学、辅助生殖及胚胎生物学无直接关联，对 ART 临床和实验室决策的可迁移性有限。","keywords":["单细胞多组学","scATAC-seq","T 细胞亚群","转录调控程序","免疫耗竭","数据整合"],"selected":1,"story_id":322,"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":"cell-rep","journal_tier":"cns-sub","journal_if":7.5,"is_mock":false,"summary_zh":"研究整合急性与慢性病毒感染应答中 CD4 与 CD8 T 细胞的单细胞多组学数据（scATAC+RNA-seq）与大规模 bulk ATAC-seq 数据集，系统刻画 T 细胞身份维持的模块化调控结构，发现不同亚群与谱系之间存在转录因子层面的调控程序复用。值得注意的是，在急性和慢性感染中均存在、对持久免疫至关重要的祖样 CD8 T 细胞呈现复合调控状态：兼具 CD8 耗竭程序与滤泡辅助性 CD4 T 细胞程序。作者据此提出可推广的计算框架与数据资源，用于解析适应性免疫机制及免疫治疗设计。原文未涉及生殖或胚胎相关对象。","summary":"T cells differentiate into functionally distinct subsets in response to pathogens, yet essential immune functions such as self-renewal, expansion, cytokine production, and cytotoxicity are common to multiple subsets and therefore must be programmed via shared regulatory mechanisms. To uncover these \"archetypal\" epigenomic programs, we integrated a single-cell multiomic (scATAC+RNA-seq) dataset of CD4 and CD8 T cells responding to acute and chronic viral infection with a comprehensive bulk ATAC-seq compendium. Our analysis reveals a modular architecture governing T cell identity, implicating distinct transcription factors in reusing regulatory programs across subsets and lineages. Notably, translationally important progenitor CD8 T cells, critical for sustained immunity and present in both acute and chronic infection, exhibit a composite regulatory state, combining a CD8 exhaustion program with a follicular helper CD4 T cell program. In sum, this resource and generalizable computational framework will aid the mechanistic dissection of adaptive immunity and immunotherapy design.","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}}