Hematopoietic loss of Y-chromosome in monocytes from heart failure patients associates with cardiac fibrosis signaling

医学 造血 纤维化 单核细胞 心脏纤维化 免疫系统 骨髓 免疫学 心力衰竭 炎症 癌症研究 病理 生物 细胞生物学 内科学 干细胞
作者
W Abplanalp,Sebastian Cremer,D John,M Merten,Bianca Schuhmacher,Igor Mačinković,Stefanie Dimmeler,Andreas M. Zeiher
出处
期刊:European Heart Journal [Oxford University Press]
卷期号:44 (Supplement_2)
标识
DOI:10.1093/eurheartj/ehad655.3079
摘要

Abstract Background Hematopoietic mosaic loss of Y chromosome (LOY) increases with age and associates with increased cardiovascular disease incidence. Furthermore, recent murine studies suggest that LOY could potentially promote cardiac fibrosis by stimulating the infiltration and activation of bone marrow-derived macrophages. Yet, specific signatures of hematopoietic LOY cells in patients with heart failure (HF) are missing. Methods and results To decode the genetic signature of circulating hematopoietic cells and assess the effects of LOY in human leukocytes, we performed single-cell RNA-sequencing (scRNA-seq) of immune cells from 10 male patients with chronic HF (mean age 67.3 years, ejection fraction 34.4%). We sorted immune cells by presence or absence of Y-chromosome-associated genes (figure 1A). Relative distribution of LOY was assessed, with monocytes having the greatest absolute count of LOY cells with no significant change in distribution among cell types. Given the abundance of monocytic LOY cells we investigated LOY monocytic cells transcriptional signatures (29810 Y-carrier monocytes, 2205 LOY monocytes) in an unbiased manner. Using a patient-specific, paired analysis, LOY monocytes showed significantly reduced expression of TGF-ß inhibiting genes (SMAD7, TGIF2) in LOY cells versus Y-carrier cells. Opposingly, from 193 upregulated genes, LOY cells showed elevated markers associated with monocyte/macrophage-mediated tissue damage and pro-fibrotic cardiac remodelling (S100A8, CLEC4D, TLR2). Gene ontology terms derived from upregulated genes in LOY cells further supported a mechanistic link to cardiac fibrosis by calling terms associated with TLR signaling, which are known to enhance cardiac fibrosis. (figure 1B). Conclusion This is the first study to decipher the genetic signature of LOY monocytes in HF patients. Our results considerably extend very recent experimental findings in mice that LOY sensitizes macrophages to enhanced profibrotic signaling. Diminished TGF-ß inhibitory molecules and enhanced TLR signaling may contribute to the aggravation of heart failure by LOY in patients with HF.HF mLOY scRNA-seq
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
中和皇极应助iday采纳,获得10
刚刚
7777777完成签到,获得积分10
刚刚
1秒前
3秒前
4秒前
思维隋发布了新的文献求助10
6秒前
幼汁汁鬼鬼完成签到,获得积分10
8秒前
10秒前
11秒前
11秒前
Prillision发布了新的文献求助10
14秒前
健哥完成签到,获得积分10
14秒前
catherine完成签到,获得积分10
15秒前
Rondab应助Zzzhou23采纳,获得30
15秒前
完美世界应助felix采纳,获得10
16秒前
17秒前
共享精神应助微笑小天鹅采纳,获得10
17秒前
18秒前
典雅的半青完成签到,获得积分10
20秒前
顺心绝山完成签到,获得积分10
22秒前
zy关注了科研通微信公众号
30秒前
30秒前
31秒前
浔xxx完成签到,获得积分20
32秒前
Mine发布了新的文献求助30
35秒前
Baili发布了新的文献求助10
37秒前
聪明伶俐的猪猪侠完成签到,获得积分10
38秒前
寒冷半雪完成签到,获得积分10
38秒前
Zjx发布了新的文献求助10
38秒前
hhhhhhhhhh完成签到 ,获得积分10
39秒前
felix发布了新的文献求助10
40秒前
40秒前
中和皇极应助明亮芯采纳,获得10
42秒前
科研通AI2S应助安徒采纳,获得10
42秒前
44秒前
45秒前
46秒前
慕青应助感谢大家采纳,获得10
47秒前
愿不负丶完成签到 ,获得积分10
49秒前
heavennew发布了新的文献求助10
49秒前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
Indomethacinのヒトにおける経皮吸収 400
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 370
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
Aktuelle Entwicklungen in der linguistischen Forschung 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3993371
求助须知:如何正确求助?哪些是违规求助? 3534027
关于积分的说明 11264545
捐赠科研通 3273794
什么是DOI,文献DOI怎么找? 1806170
邀请新用户注册赠送积分活动 883016
科研通“疑难数据库(出版商)”最低求助积分说明 809652