Details for: CL2000046

Cell ID: CL2000046

Cell Name: ventricular cardiac muscle cell

Description: Any cardiac muscle cell that is part of a cardiac ventricle.

Selected Context(s): Overall

Gene Significance Landscape

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Score:
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Genes

Contexts:

Cell Significance Index (CSI) is uniquely calculated to reveal cell-specific gene markers. More info here

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for ventricular cardiac muscle cell within the selected context(s).

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for ventricular cardiac muscle cell. Higher scores indicate a stronger, more significant difference in expression.
(Previously described as "Fold Change", but now represents Cliff's Delta × –log10(p).)

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for ventricular cardiac muscle cell. Higher scores indicate a stronger, more significant difference in expression.
Average CSI: csi sum / gene count
Cell network configuration

This network visualizes key genes for ventricular cardiac muscle cell. It primarily includes:
1. Top genes highly significant for this cell (Num. Top Cell Genes - based on the 'Min. CSI' setting).
2. Any additional specific 'Context Genes' you add below.
The final network is a combined view. Choose an Interaction Source (pathways or protein interactions) and optionally compare CSI scores with a Baseline Cell Type.

Maximum number of selected genes.
Select a context for the baseline cell.
Select a context for the target cell.
Target Cell for CSI:  ventricular cardiac muscle cell (CL2000046)

 Legend
Nodes (Genes):
 Query Gene
Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
 Very High
 High
 Medium
 Low
 Very Low
 N/A or Not Sig.
Edges (Interactions):
 STRING (Protein-Protein)
 ONTOLOGY (Shared Pathway)
 Colors vary by pathway category; default arrow applies.

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## Summary The [ventricular cardiac muscle cell](/details-cell/CL2000046) is a highly specialized, terminally differentiated cardiomyocyte responsible for the powerful, coordinated contractions of the heart's ventricles. The gene significance profile for this cell type is overwhelmingly dominated by two core functional modules: the protein machinery of the contractile sarcomere and the components of mitochondrial oxidative phosphorylation. The high expression specificity, indicated by top `csi_z` scores for genes such as the myosin light chain [MYL3](/details-gene/4634), troponin T [TNNT2](/details-gene/7139), and cardiac actin [ACTC1](/details-gene/70), establishes that the cell's identity is defined by unique isoforms of its structural and contractile apparatus. This is coupled with an equally specific signature of genes involved in energy production, such as [NDUFA4](/details-gene/4697) and multiple cytochrome c oxidase subunits, highlighting the cell's extreme metabolic demand to fuel continuous mechanical work. ## Key Characteristics and Function Analysis of the most significant genes in the **Overall** context reveals a cellular program finely tuned for contraction and energy metabolism. * **Contractile and Structural Machinery:** The most specific markers are integral components of the sarcomere. Genes such as [MYL3](/details-gene/4634), [TNNT2](/details-gene/7139), [TNNC1](/details-gene/7134), [ACTC1](/details-gene/70), and [TCAP](/details-gene/8557) all exhibit exceptionally high CSI (Z-SCORE) values. These genes encode ventricular-specific isoforms of myosin, troponin, actin, and the Z-disc protein telethonin, respectively. This isoform specificity is critical for the unique electrophysiological and mechanical properties of ventricular muscle compared to atrial or skeletal muscle. The high significance of [MYOZ2](/details-gene/51778), a Z-line protein that binds calcineurin, further suggests a tight integration of contractile structure with signaling pathways governing hypertrophy. * **High-Capacity Aerobic Respiration:** A substantial number of top markers are essential for mitochondrial function, underscoring the cell's profound reliance on oxidative phosphorylation for ATP synthesis. This includes numerous subunits of the electron transport chain: * **Complex I:** [NDUFA4](/details-gene/4697) * **Complex III:** [UQCRH](/details-gene/7388), [UQCRB](/details-gene/7381) * **Complex IV (Cytochrome c oxidase):** [COX7C](/details-gene/1350), [COX6C](/details-gene/1345), [COX4I1](/details-gene/1327), [COX5B](/details-gene/1329), [COX7A2](/details-gene/1347) * **Complex V (ATP synthase):** [ATP5MK](/details-gene/84833), [ATP5PF](/details-gene/522), [ATP5ME](/details-gene/521), [ATP5F1E](/details-gene/514) The high specificity of this entire cohort of genes suggests a precisely assembled metabolic engine tailored for the relentless energy demands of cardiac contraction. The prominence of [LDHB](/details-gene/3945) is also consistent with a preference for aerobic metabolism, facilitating the conversion of lactate to pyruvate for entry into the TCA cycle. * **Anti-Markers and Cellular State:** The least significant genes provide insight into functions that are not characteristic of this cell type. The low to negative CSI scores for multiple genes involved in mRNA splicing and processing (e.g., [DDX5](/details-gene/1655), [SRSF5](/details-gene/6430), [HNRNPU](/details-gene/3192)) and histone variants like [H3-3B](/details-gene/3021) may reflect the stable, terminally differentiated state of these cells, which have limited proliferative capacity and potentially a more streamlined transcriptional and post-transcriptional regulation landscape compared to more dynamic cell types. ## Clinical Significance and Contextual Roles Although this analysis is based on an **Overall** context without a direct disease comparison, the top marker genes for the [ventricular cardiac muscle cell](/details-cell/CL2000046) are centrally implicated in a range of cardiovascular diseases. * **Cardiomyopathies:** Mutations in the highly specific sarcomeric genes are well-established causes of inherited cardiomyopathies. For example, variants in [TNNT2](/details-gene/7139), [MYL3](/details-gene/4634), and [ACTC1](/details-gene/70) are linked to hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM). The data strongly affirm that the cell's core identity is intertwined with its primary axes of pathology. * **Heart Failure and Ischemic Injury:** The profound reliance on a specific set of mitochondrial proteins makes these cells particularly vulnerable to metabolic stress and ischemia. Dysregulation or damage to components of the electron transport chain, such as the highly ranked COX and ATP synthase subunits, is a known contributor to the energy deficit observed in heart failure. The specific expression profile identified here could serve as a reference for studying mitochondrial dysfunction in cardiac pathology. * **Regulation of Cardiac Function:** The high specificity of genes like [MYOZ2](/details-gene/51778) points to key regulatory hubs. As a binding partner of calcineurin, [MYOZ2](/details-gene/51778) is positioned to mediate hypertrophic signals in response to pathological stress, making it a potential therapeutic target for modulating cardiac remodeling. ## Potential Mechanisms and Research Directions 1. **Hypothesis: The metabolic signature of a ventricular cardiomyocyte is as defining as its contractile signature, and this metabolic specialization creates a key vulnerability.** * **Surprising Findings:** The expression specificity (`csi_z`) of mitochondrial respiratory chain components (e.g., [NDUFA4](/details-gene/4697), [COX7C](/details-gene/1350)) is quantitatively comparable to that of canonical muscle-defining proteins like [MYL3](/details-gene/4634). This suggests that the cell's identity is not just "contractile" but "aerobically contractile," and that its unique metabolic machinery is not merely supportive but a core defining feature. * **Testable Questions:** In induced pluripotent stem cell (iPSC)-derived cardiomyocytes, does silencing of ventricular-specific ETC subunit isoforms (e.g., [COX7A2](/details-gene/1347)) and replacement with more ubiquitous isoforms impair the ability to sustain rhythmic contractions under high metabolic load or when using fatty acids as a primary fuel source? 2. **Hypothesis: Specialized RNA-binding and translational control proteins are critical for maintaining long-term proteostasis of the sarcomeric and mitochondrial machinery in non-dividing ventricular cardiomyocytes.** * **Surprising Findings:** Alongside the expected structural and metabolic genes, the high specificity of [YBX1](/details-gene/4904), a protein involved in regulating transcription and translation, is unexpected. Its prominence suggests an active, specialized post-transcriptional regulatory layer is essential for maintaining the precise stoichiometry of the vast number of proteins required for cell function over a lifetime. * **Testable Questions:** Does cardiac-specific conditional knockout of [YBX1](/details-gene/4904) in an adult mouse model lead to the progressive disorganization of myofibrils and mitochondrial cristae, and does ribosome profiling reveal a specific failure to efficiently translate mRNAs encoding sarcomeric and mitochondrial proteins?