TY -的T1 Single-Nucleus染色质易访问性识别的一个关键角色TWIST1 IPF Myofibroblast活动JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00474 -2022欧元SP - 2200474 AU -埃莉诺Valenzi盟Harinath Bahudhanapati AU -江宁谭盟特雷西Tabib AU -丹尼尔。沙利文盟Mehdi Nouraie AU -约翰Sembrat盟李凡AU -香港陈盟-西尔维亚刘盟Mauricio罗哈斯AU -奥黛丽拉法尔格AU - w . Felsher盟院长港区t Tran AU -丹尼尔·J·卡斯AU -罗伯特Lafyatis Y1 - 2023/01/01 UR - //www.qdcxjkg.com/content/early/2023/04/27/13993003.00474 2022. -抽象N2 -背景特发性肺纤维化(IPF) myofibroblasts纤维化和架构的关键效应物变形由细胞外基质过度沉积和他们获得的收缩能力。单细胞RNA-sequencing (scRNA-seq)精确定义了IPF myofibroblast转录组,但识别关键转录因子(TF)活动,这种方法是不精确的。方法执行single-nucleus ATAC测序(snATAC-seq)在肺移植患者IPF (n = 3)和捐助控制(n = 2)和集成与一个更大的scRNA-seq数据集(n = 10 IPF 8控制)来识别不同访问染色质区域和丰富TF图案肺内细胞群。我们对肺成纤维细胞进行RNA-sequencing bleomycin-injured Twist1-overexpressing COL1A2 Cre-ER老鼠检查改变fibrosis-relevant通路后Twist1 collagen-producing细胞过度。结果TWIST1和其他E-box TF图案,大大丰富了在开放的染色质IPF myofibroblasts相比都IPF non-myogenic (adj假定值= 1.82 e-35 Log2FC = 8.909)和控制成纤维细胞(adj假定值= 3.72即使Log2FC = 8.975)。TWIST1表达式在IPF myofibroblasts选择性地调节(adj假定值= 1.41 e-24 Log2FC = 3.136),两个地区的TWIST1在IPF myofibroblasts显著增加的可访问性。过度的Twist1 COL1A2-expressing bleomycin-injured小鼠成纤维细胞基因导致增加胶原蛋白的合成和upregulation IPF myofibroblasts丰富染色质可访问性。结论我们的研究利用人类multiomic单细胞分析结合体内小鼠疾病模型确认关键监管功能TWIST1 IPF myofibroblast活动在肺纤维化。理解全球开放TWIST1过程和其他E-box TF主题管理myofibroblast分化可能确定新的治疗纤维化肺疾病的干预措施。FootnotesThis手稿最近发表在《欧洲呼吸杂志》上。这里发表周全之前接受的形式排版,我们的生产团队。 After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Lafyatis reports the following conflicts of interest outside the scope of work of this manuscript: R.L. has served as a consultant for Pfizer, Bristol Myers Squibb, Boehringer-Ingleheim, Formation, Sanofi, Boehringer-Mannheim, Merck and Genentech/Roche, and holds or recently had research grants from Corbus, Formation, Moderna, Regeneron, Pfizer and Kiniksa. He holds equity in Thirona.Conflict of interest: All other authors report no relevant conflicts of interest. ER -