Coronary blood vessels from distinct origins converge to equivalent states during mouse and human development (Human)
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PROVIDER: PRJNA880315 | ENA |
REPOSITORIES: ENA
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Project description:Coronary blood vessels from distinct origins converge to equivalent states during mouse and human development
| PRJNA880310 | ENA
Project description:Coronary blood vessels from distinct origins converge to equivalent states during mouse and human development (Mouse)
| PRJNA880308 | ENA
Project description:Most cell fate trajectories during development follow a diverging, tree-like branching pattern, but the opposite can occur when distinct progenitors contribute to the same cell type. During this convergent differentiation, it is unknown if cells ‘remember’ their origins transcription- ally or whether this influences cell behavior. Most coronary blood vessels of the heart develop from two different progenitor sources- the endocardium (Endo) and sinus venosus (SV)—but whether transcriptional or functional differences related to origin are retained is unknown. We addressed this by combining lineage tracing with single-cell RNA sequencing (scRNAseq) in embryonic and adult mouse hearts. Shortly after coronary development begins, capillary endothelial cells (ECs) transcriptionally segregated into two states that retained progenitor-specific gene expression. Later in development, when the coronary vasculature is well established but still remodeling, capillary ECs again segregated into two populations, but transcriptional differences were primarily related to tissue localization rather than lineage. Specifically, ECs in the heart septum expressed genes indic- ative of increased local hypoxia and decreased blood flow. Adult capillary ECs were more homoge- neous with respect to both lineage and location. In agreement, SV- and Endo-derived ECs in adult hearts displayed similar responses to injury. Finally, scRNAseq of developing human coronary vessels indicated that the human heart followed similar principles. Thus, over the course of development, transcriptional heterogeneity in coronary ECs is first influenced by lineage, then by location, until heterogeneity declines in the homeostatic adult heart. These results highlight the plasticity of ECs during development, and the validity of the mouse as a model for human coronary development.
2022-09-20 | GSE213275 | GEO
Project description:Most cell fate trajectories during development follow a diverging, tree-like branching pattern, but the opposite can occur when distinct progenitors contribute to the same cell type. During this convergent differentiation, it is unknown if cells ‘remember’ their origins transcription- ally or whether this influences cell behavior. Most coronary blood vessels of the heart develop from two different progenitor sources- the endocardium (Endo) and sinus venosus (SV)—but whether transcriptional or functional differences related to origin are retained is unknown. We addressed this by combining lineage tracing with single-cell RNA sequencing (scRNAseq) in embryonic and adult mouse hearts. Shortly after coronary development begins, capillary endothelial cells (ECs) transcriptionally segregated into two states that retained progenitor-specific gene expression. Later in development, when the coronary vasculature is well established but still remodeling, capillary ECs again segregated into two populations, but transcriptional differences were primarily related to tissue localization rather than lineage. Specifically, ECs in the heart septum expressed genes indic- ative of increased local hypoxia and decreased blood flow. Adult capillary ECs were more homoge- neous with respect to both lineage and location. In agreement, SV- and Endo-derived ECs in adult hearts displayed similar responses to injury. Finally, scRNAseq of developing human coronary vessels indicated that the human heart followed similar principles. Thus, over the course of development, transcriptional heterogeneity in coronary ECs is first influenced by lineage, then by location, until heterogeneity declines in the homeostatic adult heart. These results highlight the plasticity of ECs during development, and the validity of the mouse as a model for human coronary development.
2022-09-20 | GSE213274 | GEO
Project description:Most cell fate trajectories during development follow a diverging, tree-like branching pattern, but the opposite can occur when distinct progenitors contribute to the same cell type. During this convergent differentiation, it is unknown if cells 'remember' their origins transcriptionally or whether this influences cell behavior. Most coronary blood vessels of the heart develop from two different progenitor sources-the endocardium (Endo) and sinus venosus (SV)-but whether transcriptional or functional differences related to origin are retained is unknown. We addressed this by combining lineage tracing with single-cell RNA sequencing (scRNAseq) in embryonic and adult mouse hearts. Shortly after coronary development begins, capillary endothelial cells (ECs) transcriptionally segregated into two states that retained progenitor-specific gene expression. Later in development, when the coronary vasculature is well established but still remodeling, capillary ECs again segregated into two populations, but transcriptional differences were primarily related to tissue localization rather than lineage. Specifically, ECs in the heart septum expressed genes indicative of increased local hypoxia and decreased blood flow. Adult capillary ECs were more homogeneous with respect to both lineage and location. In agreement, SV- and Endo-derived ECs in adult hearts displayed similar responses to injury. Finally, scRNAseq of developing human coronary vessels indicated that the human heart followed similar principles. Thus, over the course of development, transcriptional heterogeneity in coronary ECs is first influenced by lineage, then by location, until heterogeneity declines in the homeostatic adult heart. These results highlight the plasticity of ECs during development, and the validity of the mouse as a model for human coronary development.
| S-EPMC8673841 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-09-20 | GSE213276 | GEO
Project description:Evaluation of transcriptional regulation in Coronary artery disease patients with and without collateral artery vessels.
2006-03-10 | E-MEXP-564 | biostudies-arrayexpress
Project description:As cardiac regeneration requires new coronary vessels, exploring the underlying mechanisms behind revascularization will facilitate the development of regenerative therapies for heart failure. Although multiple tissues and chemokines likely orchestrate coronary formation, the interaction between coronary growth and guidance cues remains unclear. Here, by applying single-cell RNA-sequencing (scRNA-seq) analysis, we examined gene expression in zebrafish epicardial cells during coronary vascularization and identified hapln1a-expressing epicardial cells enriched with vascular-regulating genes. Fluorescence reporter assays indicated hapln1a+ cells not only envelop coronary vessels, but also form cellular shear structures in ahead of coronary tips. Live imaging analyses demonstrated coronary growth along the pre-formed shears, with depletion of hapln1a+ cells blocking this growth. Further, we found hapln1a+ cells also pre-lead coronary tips in the regenerating area and hapln1a+ cell loss inhibits coronary revascularization. To characterize the molecular nature of hapln1a+ cells during coronary growth, we profiled hapln1a+ cells in juvenile and regenerating hearts and detected expression of the cell adhesion and migration regulator serpine1 in hapln1a+ cells adjacent to coronary tips. Pharmacological inhibition of serpine1 function blocked coronary vascularization and revascularization. Altogether, our studies reveal that hapln1a+ cells are required for coronary production during heart morphogenesis and regeneration, by establishing a microenvironment to facilitate guided coronary growth.
2023-05-26 | GSE216647 | GEO
Project description:As cardiac regeneration requires new coronary vessels, exploring the underlying mechanisms behind revascularization will facilitate the development of regenerative therapies for heart failure. Although multiple tissues and chemokines likely orchestrate coronary formation, the interaction between coronary growth and guidance cues remains unclear. Here, by applying single-cell RNA-sequencing (scRNA-seq) analysis, we examined gene expression in zebrafish epicardial cells during coronary vascularization and identified hapln1a-expressing epicardial cells enriched with vascular-regulating genes. Fluorescence reporter assays indicated hapln1a+ cells not only envelop coronary vessels, but also form cellular shear structures in ahead of coronary tips. Live imaging analyses demonstrated coronary growth along the pre-formed shears, with depletion of hapln1a+ cells blocking this growth. Further, we found hapln1a+ cells also pre-lead coronary tips in the regenerating area and hapln1a+ cell loss inhibits coronary revascularization. To characterize the molecular nature of hapln1a+ cells during coronary growth, we profiled hapln1a+ cells in juvenile and regenerating hearts and detected expression of the cell adhesion and migration regulator serpine1 in hapln1a+ cells adjacent to coronary tips. Pharmacological inhibition of serpine1 function blocked coronary vascularization and revascularization. Altogether, our studies reveal that hapln1a+ cells are required for coronary production during heart morphogenesis and regeneration, by establishing a microenvironment to facilitate guided coronary growth.
2023-05-26 | GSE216648 | GEO
Project description:As cardiac regeneration requires new coronary vessels, exploring the underlying mechanisms behind revascularization will facilitate the development of regenerative therapies for heart failure. Although multiple tissues and chemokines likely orchestrate coronary formation, the interaction between coronary growth and guidance cues remains unclear. Here, by applying single-cell RNA-sequencing (scRNA-seq) analysis, we examined gene expression in zebrafish epicardial cells during coronary vascularization and identified hapln1a-expressing epicardial cells enriched with vascular-regulating genes. Fluorescence reporter assays indicated hapln1a+ cells not only envelop coronary vessels, but also form cellular shear structures in ahead of coronary tips. Live imaging analyses demonstrated coronary growth along the pre-formed shears, with depletion of hapln1a+ cells blocking this growth. Further, we found hapln1a+ cells also pre-lead coronary tips in the regenerating area and hapln1a+ cell loss inhibits coronary revascularization. To characterize the molecular nature of hapln1a+ cells during coronary growth, we profiled hapln1a+ cells in juvenile and regenerating hearts and detected expression of the cell adhesion and migration regulator serpine1 in hapln1a+ cells adjacent to coronary tips. Pharmacological inhibition of serpine1 function blocked coronary vascularization and revascularization. Altogether, our studies reveal that hapln1a+ cells are required for coronary production during heart morphogenesis and regeneration, by establishing a microenvironment to facilitate guided coronary growth.
2023-05-26 | GSE216646 | GEO