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

ABSTRACT: The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its important 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 and show that they consist of three subtypes of pacemaker cells, including 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 with a functional pacemaker phenotype. This sinoatrial node pacemaker cell surface marker is highly valuable for stem cell-based disease modelling, drug discovery, cell replacement therapies, as well as the delivery of therapeutics to sinoatrial node cells in vivo using antibody-drug conjugates.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279630 | GEO | 2024/10/30

REPOSITORIES: GEO

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Project description:This a model from the article: A mathematical model of a rabbit sinoatrial node cell. Demir SS, Clark JW, Murphey CR, Giles WR. Am J Physiol 1994 Mar;266(3 Pt 1):C832-52 8166247 , Abstract: A mathematical model for the electrophysiological responses of a rabbit sinoatrial node cell that is based on whole cell recordings from enzymatically isolated single pacemaker cells at 37 degrees C has been developed. The ion channels, Na(+)-K+ and Ca2+ pumps, and Na(+)-Ca2+ exchanger in the surface membrane (sarcolemma) are described using equations for these known currents in mammalian pacemaker cells. The extracellular environment is treated as a diffusion-limited space, and the myoplasm contains Ca(2+)-binding proteins (calmodulin and troponin). Original features of this model include 1) new equations for the hyperpolarization-activated inward current, 2) assessment of the role of the transient-type Ca2+ current during pacemaker depolarization, 3) inclusion of an Na+ current based on recent experimental data, and 4) demonstration of the possible influence of pump and exchanger currents and background currents on the pacemaker rate. This model provides acceptable fits to voltage-clamp and action potential data and can be used to seek biophysically based explanations of the electrophysiological activity in the rabbit sinoatrial node cell. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Demir SS, Clark JW, Murphey CR, Giles WR. (1994) - version01 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@aukland.ac.nz The University of Auckland The Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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

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