Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging.
Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging.
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DOI：
10.1093/procel/pwac038
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发表时间：
2023-04-21
期刊：
影响因子：
21.1
通讯作者：
Qu, Jing
中科院分区：
文献类型：
--
作者：
Zhang, Yiyuan;Zheng, Yandong;Wang, Si;Fan, Yanling;Ye, Yanxia;Jing, Yaobin;Liu, Zunpeng;Yang, Shanshan;Xiong, Muzhao;Yang, Kuan;Hu, Jinghao;Che, Shanshan;Chu, Qun;Song, Moshi;Liu, Guang-Hui;Zhang, Weiqi;Ma, Shuai;Qu, Jing
老龄化是心血管疾病的主要危险因素，心血管疾病是老年人口死亡的主要原因。然而，心脏衰老背后的细胞类型特异性变化还远不清楚。在这里，我们对年轻和老年食蟹猴的左心室进行了单核RNA测序分析，以确定与年龄相关的不同细胞类型的细胞成分变化和转录变化。我们发现，衰老的心肌细胞经历了细胞数量的急剧减少和转录谱的剧烈波动。通过转录调控网络分析，我们确定Foxp1是器官发育中的核心转录因子，是老年心肌细胞中的关键下调因子，伴随着与心功能和心脏疾病相关的Foxp1靶基因的异常调控。一直以来，Foxp1的缺失导致人类胚胎干细胞来源的心肌细胞的肥大和衰老表型。总之，我们的发现描绘了单细胞分辨率下心脏老化的细胞和分子图景，并确定了灵长类心脏老化的驱动因素和干预心脏老化和相关疾病的潜在靶点。
Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.4
作者：
Hu, Danli;Dong, Ruolan;Tu, Ling
通讯作者：
Tu, Ling
影响因子：
20.1
作者：
Abdellatif, Mahmoud;Sedej, Simon;Kroemer, Guido
通讯作者：
Kroemer, Guido
SIRT7 作为异染色质稳定剂对抗人类干细胞衰老
影响因子：
21.1
作者：
Bi, Shijia;Liu, Zunpeng;Qu, Jing
通讯作者：
Qu, Jing
影响因子：
10.8
作者：
Abplanalp, Wesley T.;John, David;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie