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单细胞转录组分析揭示 CD34 作为人心房结起搏心肌细胞的标志物。

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

机构信息

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

出版信息

Nat Commun. 2024 Nov 27;15(1):10206. doi: 10.1038/s41467-024-54337-4.

DOI:10.1038/s41467-024-54337-4
PMID:39604360
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11603134/
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.

摘要

窦房结调节着人的一生的心率。这个主要起搏器的失灵会导致危及生命的缓慢心率。尽管它的功能至关重要，但人类窦房结的细胞和分子组成仍未得到解决。特别是，还没有报道用于识别和分离窦房结起搏细胞的细胞表面标记物。在这里，我们使用胎儿和人多能干细胞衍生的窦房结细胞的单细胞/核 RNA 测序来揭示它们由三种起搏细胞亚型组成：核心起搏细胞、窦房结细胞和过渡细胞。我们的研究确定了一系列窦房结起搏标记物，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对 CD34 细胞进行分选，可以富集具有功能性起搏表型的窦房结细胞。这种窦房结起搏细胞表面标记物对于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-药物偶联物将治疗药物靶向递送到体内窦房结细胞非常有价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/e8385b3bcc6a/41467_2024_54337_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/c36fb3a1b029/41467_2024_54337_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/f39397474cab/41467_2024_54337_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/4743453a05df/41467_2024_54337_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/41528df46e1a/41467_2024_54337_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/e7566350fab0/41467_2024_54337_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/c328c181c091/41467_2024_54337_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/99a380969fa7/41467_2024_54337_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/e8385b3bcc6a/41467_2024_54337_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/c36fb3a1b029/41467_2024_54337_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/f39397474cab/41467_2024_54337_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/59b7fe6f0fc6/41467_2024_54337_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/4743453a05df/41467_2024_54337_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/41528df46e1a/41467_2024_54337_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/e7566350fab0/41467_2024_54337_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/c328c181c091/41467_2024_54337_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/99a380969fa7/41467_2024_54337_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da46/11603134/e8385b3bcc6a/41467_2024_54337_Fig9_HTML.jpg

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