Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2024-11-27 DOI:10.1038/s41467-024-54337-4

Amos A. Lim, Delaram Pouyabahar, Mishal Ashraf, Kate Huang, Michelle Lohbihler, Brandon M. Murareanu, Matthew L. Chang, Maggie Kwan, Faisal J. Alibhai, Thinh Tran, Amine Mazine, Michael A. Laflamme, Gary D. Bader, Zachary Laksman, Stephanie Protze

{"title":"Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes","authors":"Amos A. Lim, Delaram Pouyabahar, Mishal Ashraf, Kate Huang, Michelle Lohbihler, Brandon M. Murareanu, Matthew L. Chang, Maggie Kwan, Faisal J. Alibhai, Thinh Tran, Amine Mazine, Michael A. Laflamme, Gary D. Bader, Zachary Laksman, Stephanie Protze","doi":"10.1038/s41467-024-54337-4","DOIUrl":null,"url":null,"abstract":"<p>The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved. Particularly, no cell surface marker to identify and isolate sinoatrial node pacemaker cells has been reported. Here we use single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell-derived sinoatrial node cells to reveal that they consist of three subtypes of pacemaker cells: Core Pacemaker, Sinus Venosus, and Transitional Cells. Our study identifies a host of sinoatrial node pacemaker markers including MYH11, BMP4, and the cell surface antigen CD34. We demonstrate that sorting for CD34<sup>+</sup> cells from stem cell differentiation cultures enriches for sinoatrial node cells exhibiting a functional pacemaker phenotype. This sinoatrial node pacemaker cell surface marker is highly valuable for stem cell-based disease modeling, drug discovery, cell replacement therapies, and the targeted delivery of therapeutics to sinoatrial node cells in vivo using antibody-drug conjugates.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"27 1","pages":""},"PeriodicalIF":14.7000,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-024-54337-4","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved. Particularly, no cell surface marker to identify and isolate sinoatrial node pacemaker cells has been reported. Here we use single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell-derived sinoatrial node cells to reveal that they consist of three subtypes of pacemaker cells: Core Pacemaker, Sinus Venosus, and Transitional Cells. Our study identifies a host of sinoatrial node pacemaker markers including MYH11, BMP4, and the cell surface antigen CD34. We demonstrate that sorting for CD34⁺ cells from stem cell differentiation cultures enriches for sinoatrial node cells exhibiting a functional pacemaker phenotype. This sinoatrial node pacemaker cell surface marker is highly valuable for stem cell-based disease modeling, drug discovery, cell replacement therapies, and the targeted delivery of therapeutics to sinoatrial node cells in vivo using antibody-drug conjugates.

Abstract Image

查看原文本刊更多论文

单细胞转录组分析显示 CD34 是人类中房结起搏器心肌细胞的标志物

中房结一生都在调节心率。这一主要起搏器失灵会导致心律缓慢，危及生命。尽管其功能至关重要，但人类中房结的细胞和分子组成仍未确定。特别是，还没有关于识别和分离中房结起搏器细胞的细胞表面标记物的报道。在这里，我们利用胎儿和人类多能干细胞衍生的中房结细胞的单核/细胞 RNA 测序，揭示了它们由三种亚型起搏器细胞组成：核心起搏器细胞、静脉窦细胞和过渡细胞。我们的研究确定了一系列中房结起搏器标记，包括 MYH11、BMP4 和细胞表面抗原 CD34。我们证明，从干细胞分化培养物中分选 CD34+ 细胞可富集出表现出功能性起搏器表型的窦房结细胞。这种中房结起搏器细胞表面标志物对基于干细胞的疾病建模、药物发现、细胞替代疗法以及使用抗体-药物共轭物向体内中房结细胞靶向递送治疗药物非常有价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.