Details for: CL0002620

Cell ID: CL0002620

Cell Name: skin fibroblast

Description: A fibroblast of skin.

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

Image representation

Depiction of skin fibroblast
Courtesy of SwissBioPics

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for skin fibroblast 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 skin fibroblast. 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 skin fibroblast. 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 skin fibroblast. 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:  skin fibroblast (CL0002620)

 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 A [skin fibroblast](/details-cell/CL0002620) is a mesenchymal cell type residing within the dermis, primarily responsible for synthesizing and remodeling the extracellular matrix (ECM). The gene significance profile for this cell type suggests a state of high metabolic and biosynthetic activity. **Overall**, top markers are dominated by genes involved in fundamental cellular processes, including iron homeostasis ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)), protein synthesis ([TPT1](/details-gene/7178), [SRP14](/details-gene/6727)), and energy production ([ND1](/details-gene/4535), [COX1](/details-gene/4512)). This signature underscores the role of the [skin fibroblast](/details-cell/CL0002620) as a metabolically active "workhorse" cell, constantly maintaining the structural integrity and physiological environment of the skin. ## Key Characteristics and Function Analysis of top marker genes, ranked by expression specificity (CSI Z-Score), reveals several core functional clusters that define the [skin fibroblast](/details-cell/CL0002620). * **Iron Homeostasis and Oxidative Stress Management:** The most significant markers are the ferritin light and heavy chain genes, [FTL](/details-gene/2512) and [FTH1](/details-gene/2495). Ferritin sequesters intracellular iron, which is essential for the function of prolyl and lysyl hydroxylases involved in collagen synthesis but can also be toxic by catalyzing the formation of reactive oxygen species. The high specificity of these genes suggests that managing iron metabolism is a primary and defining function of [skin fibroblasts](/details-cell/CL0002620), likely to support ECM production while mitigating oxidative damage. * **High Transcriptional and Translational Activity:** A large number of top markers are integral to protein synthesis and regulation. This includes the general transcription factor [BTF3](/details-gene/689), the signal recognition particle component [SRP14](/details-gene/6727) involved in co-translational protein targeting, and the poly(A)-binding protein [PABPC1](/details-gene/26986), which is crucial for mRNA stability and translation initiation. The high significance of the ubiquitin genes [UBC](/details-gene/7316) and [UBB](/details-gene/7314) further indicates a robust protein quality control system necessary to handle a high rate of protein turnover. * **Bioenergetics and Mitochondrial Function:** The list of specific markers is notably enriched for genes encoded by the mitochondrial genome, including components of Complex I ([ND1](/details-gene/4535), [ND2](/details-gene/4536), [ND4](/details-gene/4538)), Complex III ([CYTB](/details-gene/4519)), and Complex IV ([COX1](/details-gene/4512)). This highlights an essential reliance on oxidative phosphorylation to generate the substantial ATP required to fuel the energy-demanding processes of protein synthesis and ECM secretion. The high expression of [GAPDH](/details-gene/2597) also points to a significant role for glycolysis in their metabolic profile. * **Calcium Signaling and Cytoskeletal Regulation:** The calcium-binding protein [S100A6](/details-gene/6277) and the myosin light chain [MYL6](/details-gene/4637) are significant markers. This is consistent with the known roles of calcium signaling in regulating fibroblast migration, contraction, and differentiation, which are critical processes during wound healing and tissue remodeling. The **Anti-Markers** profile helps to define the cell's identity by exclusion. The low significance of hematopoietic cytokines like [CSF3](/details-gene/1440) and [LIF](/details-gene/3976), as well as specific collagens such as [COL8A2](/details-gene/1296), confirms the cell's distinct mesenchymal, non-hematopoietic lineage and its specialized ECM expression profile within the skin. ## Clinical Significance and Contextual Roles The gene signature of [skin fibroblasts](/details-cell/CL0002620) provides insights into their roles in skin health, aging, and disease. **Overall**, the prominent expression of foundational metabolic and protein synthesis machinery suggests that disruptions in these core pathways could underlie fibroblast dysfunction in various pathologies. For instance, the critical role of iron metabolism, highlighted by [FTL](/details-gene/2512) and [FTH1](/details-gene/2495), is implicated in fibrotic diseases and wound healing. Dysregulation of iron can lead to increased oxidative stress, a known driver of skin aging and pathological scarring. The high significance of [HMGB1](/details-gene/3146), a protein that acts as a damage-associated molecular pattern (DAMP) when released from cells, suggests that [skin fibroblasts](/details-cell/CL0002620) may play a direct role in initiating inflammation following tissue injury. Release of [HMGB1](/details-gene/3146) could recruit immune cells and perpetuate an inflammatory state, contributing to chronic inflammatory skin conditions or aberrant wound healing. Furthermore, the presence of [ITM2B](/details-gene/9445), a gene linked to amyloidogenesis in neurodegenerative disease ([Link](https://doi.org/10.1038/21637)), is intriguing. In the skin, its function may relate to the processing and potential aggregation of ECM proteins, a process that could be relevant to age-related changes in skin structure or in diseases involving protein deposition in the dermis. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** Skin fibroblasts function as critical hubs for iron management within the dermal microenvironment, where the capacity to safely store and utilize iron is a rate-limiting factor for effective collagen synthesis and protection against oxidative stress-induced fibrosis. * **Surprising Findings:** It is notable that genes for iron storage ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)) exhibit higher expression specificity than many canonical structural ECM genes (e.g., specific collagens or elastins). This suggests that managing the co-factors and cellular stress associated with ECM production is a more defining characteristic of this cell's identity than the structural end-products themselves. * **Testable Questions:** Does targeted knockdown of [FTH1](/details-gene/2495) in human dermal [fibroblasts](/details-cell/CL0002620) lead to a decrease in procollagen hydroxylation and secretion, alongside a concomitant increase in markers for ferroptosis, when challenged with pro-fibrotic stimuli like TGF-β? 2. **Hypothesis:** The bioenergetic state of [skin fibroblasts](/details-cell/CL0002620), dictated by the coordinated expression of nuclear and mitochondrial-encoded respiratory chain genes, is a key determinant of the cell's synthetic output and its ability to respond to tissue damage. * **Surprising Findings:** The striking prominence of multiple mitochondrial DNA-encoded genes ([ND1](/details-gene/4535), [ND2](/details-gene/4536), [COX1](/details-gene/4512), etc.) as specific markers highlights a tight coupling between mitochondrial function and fibroblast identity. This suggests that the cell's phenotype is exquisitely sensitive to its energy-producing capacity, which may be a key vulnerability in age-related skin decline. * **Testable Questions:** Can the age-associated decline in ECM production by [skin fibroblasts](/details-cell/CL0002620) be reversed or mitigated by interventions that enhance mitochondrial function, and does this correlate with restored expression levels of key mitochondrial respiratory proteins like [COX1](/details-gene/4512)?