High cardiomyocyte diversity in human early prenatal heart development
Summary: Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Here, we characterized human prenatal cardiomyocytes, 6.5–7 weeks post-conception, by integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor...
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Format: | Article |
Language: | English |
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Elsevier
2023-01-01
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Series: | iScience |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222021307 |
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author | Christer Sylvén Eva Wärdell Agneta Månsson-Broberg Eugenio Cingolani Konstantinos Ampatzis Ludvig Larsson Åsa Björklund Stefania Giacomello |
author_facet | Christer Sylvén Eva Wärdell Agneta Månsson-Broberg Eugenio Cingolani Konstantinos Ampatzis Ludvig Larsson Åsa Björklund Stefania Giacomello |
author_sort | Christer Sylvén |
collection | DOAJ |
description | Summary: Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Here, we characterized human prenatal cardiomyocytes, 6.5–7 weeks post-conception, by integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information. Using a computational workflow developed to dissect cell type heterogeneity, localize cell types, and explore their molecular interactions, we identified eight types of developing cardiomyocyte, more than double compared to the ones identified in the Human Developmental Cell Atlas. These have high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles, including outflow tract, and atria, including sinoatrial node. Moreover, cardiomyocyte ligand-receptor crosstalk is mainly with non-cardiomyocyte cell types, encompassing cardiogenesis-related pathways. Thus, early prenatal human cardiomyocytes are highly heterogeneous and develop unique location-dependent properties, with complex ligand-receptor crosstalk. Further elucidation of their developmental dynamics may give rise to new therapies. |
first_indexed | 2024-04-10T21:06:35Z |
format | Article |
id | doaj.art-777de29688124b63abc1e0d72dc36412 |
institution | Directory Open Access Journal |
issn | 2589-0042 |
language | English |
last_indexed | 2024-04-10T21:06:35Z |
publishDate | 2023-01-01 |
publisher | Elsevier |
record_format | Article |
series | iScience |
spelling | doaj.art-777de29688124b63abc1e0d72dc364122023-01-22T04:41:30ZengElsevieriScience2589-00422023-01-01261105857High cardiomyocyte diversity in human early prenatal heart developmentChrister Sylvén0Eva Wärdell1Agneta Månsson-Broberg2Eugenio Cingolani3Konstantinos Ampatzis4Ludvig Larsson5Åsa Björklund6Stefania Giacomello7Department of Medicine, Karolinska Institute, Huddinge, Sweden; Corresponding authorDepartment of Medicine, Karolinska Institute, Huddinge, SwedenDepartment of Medicine, Karolinska Institute, Huddinge, SwedenCedars-Sinai, Smidt Heart Institute, Los Angeles, CA, USADepartment of Neuroscience, Karolinska Institute, Stockholm, SwedenScience for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, SwedenDepartment of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, SwedenScience for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden; Corresponding authorSummary: Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Here, we characterized human prenatal cardiomyocytes, 6.5–7 weeks post-conception, by integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information. Using a computational workflow developed to dissect cell type heterogeneity, localize cell types, and explore their molecular interactions, we identified eight types of developing cardiomyocyte, more than double compared to the ones identified in the Human Developmental Cell Atlas. These have high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles, including outflow tract, and atria, including sinoatrial node. Moreover, cardiomyocyte ligand-receptor crosstalk is mainly with non-cardiomyocyte cell types, encompassing cardiogenesis-related pathways. Thus, early prenatal human cardiomyocytes are highly heterogeneous and develop unique location-dependent properties, with complex ligand-receptor crosstalk. Further elucidation of their developmental dynamics may give rise to new therapies.http://www.sciencedirect.com/science/article/pii/S2589004222021307Biological sciencesCell biologyBioinformaticsTranscriptomics |
spellingShingle | Christer Sylvén Eva Wärdell Agneta Månsson-Broberg Eugenio Cingolani Konstantinos Ampatzis Ludvig Larsson Åsa Björklund Stefania Giacomello High cardiomyocyte diversity in human early prenatal heart development iScience Biological sciences Cell biology Bioinformatics Transcriptomics |
title | High cardiomyocyte diversity in human early prenatal heart development |
title_full | High cardiomyocyte diversity in human early prenatal heart development |
title_fullStr | High cardiomyocyte diversity in human early prenatal heart development |
title_full_unstemmed | High cardiomyocyte diversity in human early prenatal heart development |
title_short | High cardiomyocyte diversity in human early prenatal heart development |
title_sort | high cardiomyocyte diversity in human early prenatal heart development |
topic | Biological sciences Cell biology Bioinformatics Transcriptomics |
url | http://www.sciencedirect.com/science/article/pii/S2589004222021307 |
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