Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy
Ventricular chamber development involves the coordinated maturation of diverse cardiomyocyte cell populations. In the human fetal heart, single-cell and single-nucleus RNA sequencing technologies and spatial transcriptomics reveal marked regional gene expression differences. In contrast, the mouse v...
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MDPI AG
2025-06-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| author | Javier Santos-Cantador Marcos Siguero-Álvarez José Luis de la Pompa |
| author_facet | Javier Santos-Cantador Marcos Siguero-Álvarez José Luis de la Pompa |
| author_sort | Javier Santos-Cantador |
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| description | Ventricular chamber development involves the coordinated maturation of diverse cardiomyocyte cell populations. In the human fetal heart, single-cell and single-nucleus RNA sequencing technologies and spatial transcriptomics reveal marked regional gene expression differences. In contrast, the mouse ventricular wall appears more homogeneous, except for a transient hybrid cardiomyocyte population co-expressing compact (<i>Hey2</i>) and trabecular (<i>Irx3</i>, <i>Nppa, Bmp10</i>) markers, indicating a transitional lineage state. To further investigate this, we used in situ hybridization (ISH) to examine the expression of a selected set of cardiomyocyte markers in normal and left ventricular non-compaction cardiomyopathy (LVNC) mouse models. In developing mouse ventricles, the expression of key marker genes was largely restricted to two wide myocardial domains, compact and trabecular myocardium, suggesting a less complex regional organization than the human fetal heart. Other markers labeled endocardial and coronary endothelial cells rather than cardiomyocytes, differing from patterns observed in the human heart. In the LVNC model, various markers exhibited altered spatial expression, indicating that the precise regional organization of gene expression is critical for normal ventricular wall maturation. These findings underscore the critical role of spatially regulated gene programs in ventricular chamber development and point to their potential involvement in cardiomyopathy pathogenesis. |
| format | Article |
| id | doaj-art-e33ef983651749cdae239dc4700f097c |
| institution | OA Journals |
| issn | 2308-3425 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj-art-e33ef983651749cdae239dc4700f097c2025-08-20T02:21:13ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252025-06-0112622410.3390/jcdd12060224Patterning Defects in Mice with Defective Ventricular Wall Maturation and CardiomyopathyJavier Santos-Cantador0Marcos Siguero-Álvarez1José Luis de la Pompa2Intercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Calle Melchor Fernández Almagro 3, 28029 Madrid, SpainIntercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Calle Melchor Fernández Almagro 3, 28029 Madrid, SpainIntercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Calle Melchor Fernández Almagro 3, 28029 Madrid, SpainVentricular chamber development involves the coordinated maturation of diverse cardiomyocyte cell populations. In the human fetal heart, single-cell and single-nucleus RNA sequencing technologies and spatial transcriptomics reveal marked regional gene expression differences. In contrast, the mouse ventricular wall appears more homogeneous, except for a transient hybrid cardiomyocyte population co-expressing compact (<i>Hey2</i>) and trabecular (<i>Irx3</i>, <i>Nppa, Bmp10</i>) markers, indicating a transitional lineage state. To further investigate this, we used in situ hybridization (ISH) to examine the expression of a selected set of cardiomyocyte markers in normal and left ventricular non-compaction cardiomyopathy (LVNC) mouse models. In developing mouse ventricles, the expression of key marker genes was largely restricted to two wide myocardial domains, compact and trabecular myocardium, suggesting a less complex regional organization than the human fetal heart. Other markers labeled endocardial and coronary endothelial cells rather than cardiomyocytes, differing from patterns observed in the human heart. In the LVNC model, various markers exhibited altered spatial expression, indicating that the precise regional organization of gene expression is critical for normal ventricular wall maturation. These findings underscore the critical role of spatially regulated gene programs in ventricular chamber development and point to their potential involvement in cardiomyopathy pathogenesis.https://www.mdpi.com/2308-3425/12/6/224cardiac chamber developmentcellular heterogeneitypatterningcardiomyopathyLVNCMib1 |
| spellingShingle | Javier Santos-Cantador Marcos Siguero-Álvarez José Luis de la Pompa Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy Journal of Cardiovascular Development and Disease cardiac chamber development cellular heterogeneity patterning cardiomyopathy LVNC Mib1 |
| title | Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy |
| title_full | Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy |
| title_fullStr | Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy |
| title_full_unstemmed | Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy |
| title_short | Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy |
| title_sort | patterning defects in mice with defective ventricular wall maturation and cardiomyopathy |
| topic | cardiac chamber development cellular heterogeneity patterning cardiomyopathy LVNC Mib1 |
| url | https://www.mdpi.com/2308-3425/12/6/224 |
| work_keys_str_mv | AT javiersantoscantador patterningdefectsinmicewithdefectiveventricularwallmaturationandcardiomyopathy AT marcossigueroalvarez patterningdefectsinmicewithdefectiveventricularwallmaturationandcardiomyopathy AT joseluisdelapompa patterningdefectsinmicewithdefectiveventricularwallmaturationandcardiomyopathy |