Details for: CL0002399

Cell ID: CL0002399

Cell Name: CD1c-positive myeloid dendritic cell

Description: Normally represent 10-20% of peripheral blood mDCs (human). They are also CD281-positive (TLR1), CD282-positive (TLR2), CD283-positive (TLR3), CD284-positive (TLR4), CD285-positive (TLR5), CD286-positive (TLR6), CD288-positive (TLR8), and CD290-positive (TLR10) [PMID:20204387]. Upon TLR stimulation, these cells were potent producers of CXCL8 (IL-8), while producing little TNF-alpha.

Selected Context(s): Overall

Gene Significance Landscape

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Score:
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Genes

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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 CD1c-positive myeloid dendritic 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 CD1c-positive myeloid dendritic 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 CD1c-positive myeloid dendritic 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 CD1c-positive myeloid dendritic 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:  CD1c-positive myeloid dendritic cell (CL0002399)

 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 [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399) is a subset of myeloid dendritic cells known for its expression of a wide array of Toll-like receptors (TLRs) and its capacity to produce the chemokine [CXCL8](/details-gene/3576) upon stimulation. Analysis of its gene significance profile in an **Overall** context reveals a striking and defining characteristic: an exceptionally high specificity for genes involved in iron metabolism and cellular bioenergetics. The top markers are dominated by the ferritin light and heavy chains, [FTL](/details-gene/2512) and [FTH1](/details-gene/2495), alongside numerous components of the mitochondrial electron transport chain. This molecular signature suggests that beyond its established role in innate immune sensing, this cell type is highly specialized for managing iron homeostasis and maintaining a state of high metabolic readiness, likely to fuel its demanding functions in antigen presentation and inflammatory response. ## Key Characteristics and Function The functional identity of the [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399) is elucidated by several clusters of highly specific genes. * **Iron Homeostasis and Immunomodulation:** The most prominent feature of this cell is the profound specificity of the ferritin light ([FTL](/details-gene/2512)) and heavy ([FTH1](/details-gene/2495)) chains. Ferritin is critical for intracellular iron sequestration, and its high expression may serve dual roles: protecting the cell from iron-induced oxidative stress during high metabolic activity and participating in antimicrobial defense by limiting iron availability to pathogens. The specific expression of these genes, as supported by early cloning studies ([Link](https://pubmed.ncbi.nlm.nih.gov/3840162/), [Link](https://pubmed.ncbi.nlm.nih.gov/6323167/)), underscores iron metabolism as a central aspect of this cell's biology. * **High Metabolic Activity and Bioenergetics:** A large number of the top markers are directly involved in cellular respiration and energy production. These include multiple subunits of ATP synthase ([ATP5F1E](/details-gene/514), [ATP5MC2](/details-gene/517), [ATP5MG](/details-gene/10632)) and cytochrome c oxidase ([COX1](/details-gene/4512), [COX2](/details-gene/4513), [COX4I1](/details-gene/1327)), as well as a key NADH dehydrogenase subunit ([ND1](/details-gene/4535)). The high specificity of the glycolytic enzyme [GAPDH](/details-gene/2597) further supports a high energetic state. This metabolic machinery is likely essential for powering energy-intensive processes such as antigen processing, cell migration, and the synthesis of immune mediators. * **Antigen Presentation and Protein Synthesis:** As a professional antigen-presenting cell, its identity is supported by the high specificity of [B2M](/details-gene/567), an essential component of MHC class I molecules required for presenting antigens to [CD8-positive, alpha-beta T cells](/details-cell/CL0000625). This function is complemented by a suite of specific markers involved in protein synthesis and stability, such as [PABPC1](/details-gene/26986), [YBX1](/details-gene/4904), and [TPT1](/details-gene/7178), indicating a robust capacity for producing the molecules needed for immune communication. * **Cytoskeletal Dynamics:** The specific expression of cytoskeletal components like cofilin ([CFL1](/details-gene/1072)) and myosin light chain ([MYL6](/details-gene/4637)) points to a role in cell motility, phagocytosis, and the formation of immunological synapses, all critical functions for dendritic cell interaction with other immune cells. * **Defining by Exclusion:** The anti-marker data provides contrast. The low specificity score for the monocyte chemokine receptor [CCR2](/details-gene/729230) suggests a distinct identity from classical monocytes that rely heavily on this receptor for tissue infiltration. Similarly, the low specificity for [CD1B](/details-gene/910) suggests that, despite being named for its CD1c expression, a broad upregulation of the entire CD1 family is not a defining feature, pointing towards a specialized role in presenting a specific subset of lipid antigens via CD1c. ## Clinical Significance and Contextual Roles The gene signature of the [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399), analyzed in an **Overall** context, provides a baseline understanding of its potential roles in health and disease. The profound signature of ferritin ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)) is clinically significant, as ferritin levels are known to be elevated in a wide range of inflammatory conditions and infections. This suggests that [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399) could be key contributors to systemic iron dysregulation during inflammation, potentially influencing disease course by modulating both pathogen growth and the function of other immune cells. The high metabolic state, characterized by specific expression of mitochondrial and glycolytic genes, implies these cells are major energy consumers. In pathological contexts such as the tumor microenvironment, their high metabolic demand could lead to competition for nutrients with tumor cells or other immune effectors, potentially impacting anti-tumor immunity. Conversely, this metabolic "readiness" may be critical for mounting rapid and effective responses to infection or vaccination. The constitutive high expression of [B2M](/details-gene/567) reinforces their role in constant immune surveillance and their potential importance in presenting viral or tumor antigens to initiate cytotoxic T cell responses. ## Potential Mechanisms and Research Directions 1. **Hypothesis: Iron Sequestration as a Primary Effector Function** * The exceptionally high and specific expression of ferritin subunits ([FTL](/details-gene/2512) and [FTH1](/details-gene/2495)) suggests that [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399) function as key regulators of local iron homeostasis, serving as a primary antimicrobial and immunomodulatory mechanism beyond their own metabolic requirements. * **Surprising Findings:** The specificity of ferritin genes surpasses that of canonical immune function genes like [B2M](/details-gene/567), which is unexpected for proteins often associated with general metabolism. Furthermore, the high Z-score for [GAPDH](/details-gene/2597), a classic housekeeping gene, may indicate unique metabolic programming or a non-canonical role in these dendritic cells. * **Testable Question:** Does targeted knockdown of [FTH1](/details-gene/2495) in [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399) impair their ability to control the growth of iron-dependent bacteria *in vitro* or alter their capacity to polarize T cell responses? 2. **Hypothesis: A State of Metabolic "Poisedness" for Rapid Immune Response** * The coordinate high specificity of numerous mitochondrial ([COX1](/details-gene/4512), [ATP5F1E](/details-gene/514)) and glycolytic ([GAPDH](/details-gene/2597)) genes indicates that [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399) exist in a metabolically "poised" state, maintaining high baseline energy production capacity to fuel immediate, energy-demanding effector functions like cytokine release upon TLR stimulation. * **Surprising Findings:** The observation that a broad set of core metabolic genes serve as highly *specific* markers (high `csi_z`) challenges their view as simple housekeeping genes. This suggests their expression is uniquely elevated in this cell type compared to others, implying this metabolic profile is a specialized, defining feature rather than a common background activity. * **Testable Question:** Using a metabolic flux analyzer, do resting [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399) exhibit a higher basal rate of oxidative phosphorylation and glycolysis compared to other myeloid populations, and does pharmacological inhibition of these pathways disproportionately blunt their production of [CXCL8](/details-gene/3576) following TLR ligation?