GO:0061051 positive regulation of cell growth involved in cardiac muscle cell development: Regulatory Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061051 describes any process that increases the rate, frequency, or extent of cardiac muscle cell growth as the cell progresses from initial formation to a mature state.
• This term is a biological process child of positive regulation of cell growth and is specifically restricted to growth that contributes to cardiac muscle cell development.
• Key molecular drivers include epigenetic regulators, growth factor signaling pathways such as HGF/Met, and stress-responsive kinases such as ERK/MAPK.
• Dysregulation of this process is linked to cardiac hypertrophy, heart failure, and cardiotoxicity, making it a target for mechanistic and translational studies.
• CRISPR-based knockout, point mutation, knock-in, and overexpression models are powerful tools to test causality of candidate genes in cardiac muscle cell growth.
• Researchers can combine transcriptomics, microRNA profiling, and functional assays in cardiomyocyte models to dissect this GO term.
Description
GO:0061051, positive regulation of cell growth involved in cardiac muscle cell development, is a Gene Ontology biological process term that captures the upstream signals and intracellular events that increase the growth of cardiac muscle cells during their developmental maturation. This term is distinct from general cell growth because it is explicitly tied to the developmental progression of cardiomyocytes from initial formation to a mature state, a process that is essential for normal heart morphogenesis and function. Understanding this term helps researchers frame experiments on cardiac hypertrophy, regeneration, and developmental cardiotoxicity within a precise ontological context. Cardiac muscle cell growth is not a single molecular event but a coordinated outcome of growth factor signaling, transcriptional and epigenetic reprogramming, and metabolic adaptation. For example, activation of the HGF/Met pathway in neonatal mouse heart triggers gene expression programs that support cardiomyocyte growth and survival, while the ERK/MAPK cascade modulates cardiomyocyte apoptosis and cytokine release under stress. Epigenetic dimensions, including DNA methylation and histone modifications, further shape the fetal-to-adult transition of the cardiac myocyte epigenome, which directly influences growth capacity. Because GO:0061051 is a positive regulation term, it is particularly relevant for identifying gain-of-function mechanisms, therapeutic targets, and biomarkers that drive or sustain cardiac muscle cell growth. Disruption of these regulatory circuits can contribute to heart failure, as shown by downregulation of TCF19 and ATAD2 causing endothelial cell cycle arrest at the transition from cardiac hypertrophy to heart failure. This article synthesizes authoritative QuickGO annotation with real PubMed literature to provide a research-grade overview of GO:0061051, its genes, mechanisms, disease links, and experimental methods.
positive regulation of cell growth involved in cardiac muscle cell development At A Glance
| GO ID | GO:0061051 |
|---|---|
| GO term | positive regulation of cell growth involved in cardiac muscle cell development |
| Ontology | biological_process |
| Synonym | None listed in QuickGO |
| Major function | Increases the rate, frequency, or extent of cardiac muscle cell growth during developmental maturation |
| Parent term | positive regulation of cell growth |
| Related process | cardiac muscle cell development |
| Directionality | Positive regulation (upregulation) |
| Cellular context | Cardiac muscle cells (cardiomyocytes) |
What Is GO:0061051?
GO:0061051 is defined by QuickGO as any process that increases the rate, frequency, or extent of the growth of a cardiac muscle cell, where growth contributes to the progression of the cell over time from its initial formation to its mature state. In practical terms, it covers positive regulatory inputs, such as growth factor signaling, transcriptional activation, and epigenetic changes, that promote cardiomyocyte enlargement or expansion as part of normal cardiac development. It excludes negative regulation of cardiac muscle cell growth and general cell growth that is not linked to cardiac muscle cell development.
Why Is positive regulation of cell growth involved in cardiac muscle cell development Important in Cell Biology?
GO:0061051 is important because cardiac muscle cell growth is a central determinant of heart size, contractile capacity, and response to injury, and its positive regulation must be tightly controlled to avoid pathological hypertrophy or heart failure. Many signaling pathways and epigenetic regulators that modulate this process are conserved and druggable, making the term a useful entry point for target discovery in cardiovascular disease. In addition, cardiotoxicity from environmental chemicals or drugs can disrupt cardiomyocyte growth programs, as illustrated by famoxadone-cymoxanil-induced cardiotoxicity in zebrafish embryos. Therefore, researchers studying cardiac development, regeneration, and disease need a precise understanding of GO:0061051 to design informative experiments and interpret omics data.
• Defines a specific positive regulatory process that controls cardiomyocyte growth during development, distinct from general cell growth.
• Links growth factor signaling pathways such as HGF/Met to cardiac muscle cell growth and maturation.
• Connects to stress-responsive kinase cascades like ERK/MAPK that modulate cardiomyocyte apoptosis and cytokine release.
• Provides a framework for studying epigenetic reprogramming during the fetal-to-adult transition of cardiac myocytes.
• Relevant to heart failure mechanisms, including cell cycle arrest at the transition from hypertrophy to failure.
• Useful for interpreting cardiotoxicity phenotypes in model organisms such as zebrafish embryos.
• Supports research on microRNA-mediated regulation of cardiac cell growth and extracellular vesicle signaling.
• Helps contextualize neurohormonal and metabolic influences on cardiac cachexia and muscle wasting.
• Guides CRISPR-based functional genomics screens for regulators of cardiomyocyte growth.
• Enables cross-species comparison of cardiac growth programs using transcriptomic profiling.
What Happens During positive regulation of cell growth involved in cardiac muscle cell development?
Initiation by growth factor and neurohormonal signals
In simple terms: Growth factors and hormones tell the heart muscle cell to start growing.
Positive regulation of cardiac muscle cell growth is initiated by extracellular cues such as hepatocyte growth factor (HGF) acting through its receptor Met, which activates gene expression programs in neonatal mouse heart. Neurohormonal regulators, including melatonin-related pathways, can modulate cardiac cachexia and muscle wasting, indirectly influencing the metabolic environment for cardiomyocyte growth. These signals converge on intracellular cascades that prepare the cell for increased growth and maturation.
Intracellular kinase cascade activation
In simple terms: Enzymes inside the cell relay the growth signal to the nucleus.
The ERK/MAPK pathway is a key intracellular cascade that regulates cardiomyocyte apoptosis and cytokine release, and its activity can influence the balance between growth and stress responses. Activation of such kinase cascades leads to phosphorylation of transcription factors and other targets that promote cardiac muscle cell growth. Dysregulation of these cascades can shift the cell toward pathological hypertrophy or failure.
Epigenetic and transcriptional reprogramming
In simple terms: The cell changes which genes are turned on or off to support growth.
The cardiac myocyte epigenome undergoes four-dimensional changes from fetal to adult heart, including DNA methylation and histone modifications that affect growth-related gene expression. Positive regulation of cardiac muscle cell growth requires coordinated transcriptional activation of genes involved in sarcomere assembly, metabolism, and cell cycle progression. Epigenetic regulators such as TCF19 and ATAD2 have been implicated in cell cycle arrest at the transition from cardiac hypertrophy to heart failure, highlighting the importance of transcriptional control in this process.
MicroRNA and extracellular vesicle modulation
In simple terms: Small RNA molecules and vesicles fine-tune the growth response.
MicroRNA profiling of HL-1 cardiac cells-derived extracellular vesicles has revealed that miRNAs can be packaged and transferred to modulate cardiac cell growth and communication. These small non-coding RNAs can repress or enhance the expression of growth-related genes, adding another layer of positive regulation. Extracellular vesicles may thus serve as paracrine regulators of cardiac muscle cell development.
Integration with cell cycle and maturation
In simple terms: The cell decides whether to grow, divide, or mature based on all signals.
Positive regulation of cell growth involved in cardiac muscle cell development ultimately influences whether cardiomyocytes increase in size, progress through the cell cycle, or exit to a mature state. Downregulation of specific genes such as TCF19 and ATAD2 can cause cell cycle arrest, linking growth regulation to the transition from hypertrophy to heart failure. Therefore, this GO term represents an integrated outcome of multiple signaling, epigenetic, and RNA-based inputs.
Key Genes Involved in GO:0061051 positive regulation of cell growth involved in cardiac muscle cell development
The following genes and proteins have been reported in the literature to influence cardiac muscle cell growth, development, or related signaling pathways relevant to GO:0061051.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HGF | Growth factor ligand that activates Met signaling | Activates gene expression programs in neonatal mouse heart |
| Met | Receptor tyrosine kinase for HGF | Mediates HGF-induced cardiac growth signaling |
| ERK1/2 (MAPK3/MAPK1) | Kinases in the ERK/MAPK cascade | Regulate cardiomyocyte apoptosis and cytokine release |
| TCF19 | Transcription factor involved in cell cycle regulation | Downregulation causes endothelial cell cycle arrest in heart failure transition |
| ATAD2 | Chromatin remodeler and transcriptional co-regulator | Downregulation linked to cell cycle arrest in heart failure |
| Klotho | Anti-aging protein modulating FGF23 signaling | Regulates cardiomyocyte apoptosis via ERK/MAPK |
| FGF23 | Fibroblast growth factor involved in phosphate metabolism | Part of Klotho/FGF23 axis affecting cardiomyocytes |
| miRNAs (e.g., from HL-1 EVs) | Small non-coding RNAs regulating gene expression | Profiled in cardiac cell-derived extracellular vesicles |
| Epigenetic modifiers (DNMTs, HDACs) | Enzymes that modify DNA and histones | Shape the fetal-to-adult cardiac myocyte epigenome |
| Melatonin pathway components | Neurohormonal regulators of cardiac cachexia | Modulate metabolic and growth-related signaling |
| Satellite cell-related genes | Muscle stem cell regulators | Implicated in neuromuscular disorders affecting muscle growth |
| Zebrafish cardiotoxicity targets | Genes affected by famoxadone-cymoxanil | Model for chemical-induced cardiac growth disruption |
| Cell cycle regulators (e.g., cyclins) | Control progression through the cell cycle | Linked to hypertrophy-to-failure transition |
| Sarcomeric proteins | Structural components of cardiac muscle | Required for functional cardiomyocyte growth |
| Metabolic enzymes | Support energy demand during growth | Adapted during fetal-to-adult transition |
| Extracellular vesicle cargo proteins | Mediate intercellular communication | Involved in cardiac cell signaling |
How Is positive regulation of cell growth involved in cardiac muscle cell development Regulated?
GO:0061051 is regulated at multiple levels, including extracellular growth factor availability, receptor tyrosine kinase activity, intracellular kinase cascades such as ERK/MAPK, and epigenetic modifications that control gene accessibility. The HGF/Met axis provides a direct positive input by activating transcriptional programs in neonatal mouse heart. The Klotho/FGF23 axis can modulate cardiomyocyte apoptosis and cytokine release through ERK/MAPK, thereby influencing the balance between growth and stress. Epigenetic regulators, including those affected by TCF19 and ATAD2 downregulation, can impose cell cycle arrest and limit growth during the transition from cardiac hypertrophy to heart failure. MicroRNAs delivered via extracellular vesicles add another layer of post-transcriptional regulation. Neurohormonal factors such as melatonin-related pathways may also influence cardiac cachexia and muscle wasting, indirectly affecting the metabolic support for cardiomyocyte growth.
positive regulation of cell growth involved in cardiac muscle cell development and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| TCF19 | Heart failure transition from hypertrophy | Knockout or knockdown in cardiomyocyte cell lines |
| ATAD2 | Cell cycle arrest in heart failure | CRISPR knockout in cardiac cells |
| ERK/MAPK components | Cardiomyocyte apoptosis and cytokine release | Point mutation or overexpression in cardiomyocytes |
| HGF/Met | Cardiac growth signaling | Overexpression or knockout in neonatal mouse heart |
| Famoxadone-cymoxanil targets | Cardiotoxicity in zebrafish | Zebrafish embryo exposure and genetic manipulation |
Heart failure and pathological hypertrophy
Dysregulation of positive regulation of cardiac muscle cell growth can contribute to heart failure. Downregulation of TCF19 and ATAD2 causes endothelial cell cycle arrest at the transition from cardiac hypertrophy to heart failure, indicating that loss of growth-promoting regulators is associated with disease progression. The ERK/MAPK pathway, which modulates cardiomyocyte apoptosis and cytokine release, is also implicated in maladaptive cardiac remodeling. Therefore, GO:0061051-related genes are candidate targets for therapeutic intervention in heart failure.
Cardiotoxicity and developmental defects
Environmental chemicals such as famoxadone-cymoxanil can induce cardiotoxicity in zebrafish embryos, disrupting normal cardiac development and growth. Such models help identify pathways that positively regulate cardiac muscle cell growth and are vulnerable to toxic insult. These findings have implications for developmental cardiotoxicity screening and regulatory toxicology.
Cardiac cachexia and muscle wasting
Cardiac cachexia involves systemic metabolic and neurohormonal changes that lead to muscle wasting, including cardiac muscle. Melatonin and related neurohormonal regulators have been proposed to modulate these processes, potentially influencing the growth and maintenance of cardiac muscle cells. Understanding GO:0061051 in this context may reveal links between systemic metabolism and cardiomyocyte growth.
Neuromuscular disorders and satellite cell dysfunction
Muscle satellite cell dysfunction is increasingly recognized in neuromuscular disorders, which can affect muscle growth and regeneration. Although satellite cells are primarily skeletal muscle progenitors, shared mechanisms of muscle growth regulation may inform cardiac muscle research. This cross-tissue perspective highlights the broader relevance of growth regulatory pathways.
From positive regulation of cell growth involved in cardiac muscle cell development-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a candidate gene reduce cardiac muscle cell growth? | CRISPR knockout in cardiomyocyte cell lines or primary cells |
| Does a specific point mutation alter growth signaling? | Point mutation knock-in via CRISPR in cardiac cells |
| Does overexpression of a growth factor enhance cardiomyocyte growth? | Overexpression of HGF or Met in neonatal mouse heart |
| How does epigenetic regulation affect cardiac growth? | Tagged knock-in of epigenetic modifiers in cardiac myocytes |
| What miRNAs regulate cardiac cell growth? | MicroRNA profiling of HL-1 cardiac cells-derived extracellular vesicles |
| Can chemical exposure disrupt cardiac growth? | Zebrafish embryo cardiotoxicity model |
How to Study the positive regulation of cell growth involved in cardiac muscle cell development Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify growth-related transcriptional programs |
| MicroRNA profiling | Expression of small non-coding RNAs | Study EV-mediated regulation in cardiac cells |
| ATAC-seq / ChIP-seq | Chromatin accessibility and histone modifications | Map epigenetic regulation of cardiac growth |
| Western blot | Protein expression and phosphorylation | Assess ERK/MAPK activation |
| Immunofluorescence | Cell size and sarcomere organization | Measure cardiomyocyte hypertrophy |
| Zebrafish cardiotoxicity assay | Heart development and function | Evaluate chemical effects on cardiac growth |
| CRISPR knockout screening | Gene function at scale | Discover novel regulators of cardiac growth |
Transcriptomic profiling
RNA sequencing and gene expression profiling can identify genes and pathways that are differentially expressed during positive regulation of cardiac muscle cell growth. For example, gene expression profiling of HGF/Met activation in neonatal mouse heart revealed downstream targets. Such data can be integrated with GO:0061051 annotations to prioritize candidate regulators.
MicroRNA and extracellular vesicle analysis
MicroRNA profiling of HL-1 cardiac cells-derived extracellular vesicles provides a method to study post-transcriptional regulation of cardiac growth. This approach can reveal miRNAs that modulate growth-related genes and may serve as biomarkers or therapeutic agents. Combining miRNA data with target prediction and functional assays strengthens causal inference.
Epigenomic mapping
Assays such as ATAC-seq, ChIP-seq, and DNA methylation profiling can map the epigenetic landscape of cardiac myocytes across developmental stages. These methods help identify regulatory elements that control growth-related genes. The four dimensions of the cardiac myocyte epigenome from fetal to adult heart provide a framework for such studies.
Functional assays in cardiomyocyte models
Cell proliferation, hypertrophy, and apoptosis assays in cardiomyocyte cell lines or primary cells can directly measure the outcomes of positive regulation of cell growth. Zebrafish embryo models allow in vivo assessment of cardiac development and cardiotoxicity. These functional readouts complement omics data to establish causality.
How CRISPR Can Be Used to Study GO:0061051 positive regulation of cell growth involved in cardiac muscle cell development
Knockout
CRISPR knockout of candidate genes such as TCF19 or ATAD2 in cardiac cell models can test whether they are required for positive regulation of cardiac muscle cell growth. Loss-of-function studies help distinguish drivers from bystanders in growth signaling networks. Knockout models are also useful for validating hits from transcriptomic screens.
Point Mutation
Point mutation knock-in can model specific amino acid changes in kinases such as ERK/MAPK components to dissect their role in cardiomyocyte growth and apoptosis. This approach is valuable for studying gain-of-function or loss-of-function variants identified in patients or experiments. Precise point mutations allow separation of catalytic activity from scaffolding functions.
Knock-in
Tagged knock-in of epigenetic modifiers or growth factor receptors enables tracking of protein localization and interactions in cardiac cells. Knock-in of reporter genes can also monitor transcriptional activity of growth-related promoters. These models support live-cell imaging and biochemical purification.
Overexpression
Overexpression of HGF or Met in neonatal mouse heart has been used to activate cardiac growth programs. CRISPR-mediated overexpression or transgenic approaches can test sufficiency of a gene to promote cardiac muscle cell growth. Overexpression models are particularly useful for studying positive regulation in GO:0061051.
How EDITGENE Supports positive regulation of cell growth involved in cardiac muscle cell development Research
Researchers studying positive regulation of cell growth involved in cardiac muscle cell development-related genes often need to determine whether a candidate gene is causally involved in cardiomyocyte growth or simply correlated with it. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such causal experiments in cardiac cell models.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of cell growth involved in cardiac muscle cell development research.
Frequently Asked Questions About positive regulation of cell growth involved in cardiac muscle cell development
What is GO:0061051?
GO:0061051 is the Gene Ontology term for positive regulation of cell growth involved in cardiac muscle cell development, describing processes that increase the growth of cardiac muscle cells during their developmental maturation.
What genes are involved in positive regulation of cardiac muscle cell growth?
Genes such as HGF, Met, ERK/MAPK components, TCF19, ATAD2, and Klotho/FGF23 axis members have been implicated in cardiac muscle cell growth regulation.
How is cardiac muscle cell growth regulated?
It is regulated by growth factor signaling, kinase cascades like ERK/MAPK, epigenetic modifications, and microRNAs.
What diseases are linked to GO:0061051?
Heart failure, pathological hypertrophy, cardiotoxicity, and cardiac cachexia have been associated with dysregulation of cardiac muscle cell growth.
What model systems are used to study cardiac muscle cell growth?
Cardiomyocyte cell lines, neonatal mouse heart, and zebrafish embryos are commonly used models.
How can CRISPR help study positive regulation of cardiac muscle cell growth?
CRISPR knockout, point mutation, knock-in, and overexpression can test causality of candidate genes in cardiac growth.
What is the role of ERK/MAPK in cardiac muscle cell growth?
ERK/MAPK signaling modulates cardiomyocyte apoptosis and cytokine release, influencing the balance between growth and stress.
What is the role of epigenetics in cardiac muscle cell development?
Epigenetic changes such as DNA methylation and histone modifications shape the fetal-to-adult transition and regulate growth-related genes.
Are there microRNAs that regulate cardiac cell growth?
Yes, microRNAs packaged in extracellular vesicles from HL-1 cardiac cells have been profiled and can modulate cardiac cell communication.
What is the HGF/Met pathway's role in cardiac growth?
HGF/Met activation triggers gene expression programs in neonatal mouse heart that support cardiac growth and survival.
Conclusion
GO:0061051, positive regulation of cell growth involved in cardiac muscle cell development, is a critical biological process that integrates growth factor signaling, kinase cascades, epigenetic reprogramming, and microRNA regulation to control cardiomyocyte maturation. Its dysregulation is linked to heart failure, cardiotoxicity, and cardiac cachexia, making it a valuable focus for cardiovascular research. By leveraging CRISPR-based models and multi-omics methods, researchers can dissect the causal roles of specific genes and pathways in this process.
References
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