{"id":370,"title":"Integration of ATAC- and RNA-sequencing identifies chromatin and transcriptomic signatures in classical and non-classical zebrafish osteoblasts and indicates mechanisms of entpd5a regulation","title_zh":"整合ATAC与RNA测序鉴定经典与非经典斑马鱼成骨细胞的染色质及转录组特征并揭示entpd5a调控机制","url":"https://pubmed.ncbi.nlm.nih.gov/42945310","doi":"10.7554/elife.100230","pmid":"42945310","journal":"Elife","kind":"paper","lang":"en","published_at":"2026-10-27T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Petratou K","Stehling M","Müller F","Schulte-Merker S"],"primary_topic":"ethics-policy","topics":[{"slug":"omics-methods","score":5.0,"hits":["rna-seq","transcriptomic"]},{"slug":"ethics-policy","score":4.0,"hits":["regulation"]},{"slug":"animal-models","score":3.2,"hits":["zebrafish"]},{"slug":"repro-genetics","score":1.0,"hits":["atac-seq"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":47.0,"final_score":53.0,"score_dims":{"novelty":68,"rigor":72,"impact":32,"relevance":20,"translation":18},"recommend_reason":"方法学扎实（转基因分选＋ATAC/RNA-seq整合＋启动子实验验证），但研究对象为斑马鱼骨骼发育，与生殖医学、辅助生殖及胚胎多组学（配子/植入前胚胎）关联很弱，仅对比较发育与多组学技术路线有间接参考价值，不建议作为生殖领域优先阅读。","keywords":["斑马鱼","成骨细胞","ATAC-seq","RNA-seq","entpd5a","染色质调控"],"selected":0,"story_id":304,"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":"elife","journal_tier":"general-top","journal_if":6.4,"is_mock":false,"summary_zh":"研究利用新构建的转基因斑马鱼系，从胚胎中分选出经典成骨细胞（与哺乳动物同源）与非经典成骨细胞（脊索鞘细胞），联合ATAC-seq与RNA-seq分别及整合分析，比较两类骨骼细胞的染色质开放性与转录组差异。结果显示Dlx家族因子主要参与经典成骨细胞调控，而Hox家族因子经非经典成骨细胞调控脊柱骨化。作者还对entpd5a启动子进行了数据驱动分析，实验验证了ATAC-seq结果，并提出骨化过程中entpd5a复杂表达模式的时空调控机制（启动子/增强子互作）假说，为骨发育研究提供资源性数据。","summary":"Two types of osteoblasts are required to assemble the zebrafish embryonic skeleton: classical osteoblasts homologous to the mammalian cell and notochord sheath cells which serve as non-classical osteoblasts. The gene entpd5a is critically required for ossification via both types of osteoblasts. Despite the indispensability of zebrafish models in vertebrate research, the genetic regulation of bone formation, as well as mechanisms of transcriptional control of entpd5a, remains largely unknown. Here, using a newly generated transgenic line, we isolate classical and non-classical osteoblasts from zebrafish embryos and performed both assay for transposase-accessible chromatin (ATAC)-seq and RNA-seq. We analysed results independently and integratively to understand those chromatin dynamics and accompanying transcriptomic changes that occur in different skeletal cell types. We show that although Dlx family factors are playing important roles in classical osteoblast regulation, Hox family factors are involved in governing spinal ossification via non-classical osteoblasts. We further present a resource-driven analysis of the entpd5a promoter, experimentally validating the ATAC-seq dataset and proposing mechanisms of regulating the complex entpd5a expression pattern during zebrafish osteogenesis. Our results thus provide a necessary comprehensive resource for the field of bone development and indicate spatio-temporally regulated promoter/enhancer interactions taking place in the entpd5a locus.","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}}