Details for: CL4033013

Cell ID: CL4033013

Cell Name: suprabasal keratinocyte

Description: A keratinocyte that resides in the epidermal suprabasal layer and expresses differentiation markers, including keratin 1 and keratin 10, in both humans and mice. In human interfollicular epidermis, this cell retains proliferative capacity and possesses retrodifferentiation potential, acquiring basal-like properties during wound healing or basement membrane contact.

Selected Context(s): Overall

Gene Significance Landscape

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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 suprabasal keratinocyte 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 suprabasal keratinocyte. 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 suprabasal keratinocyte. 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 suprabasal keratinocyte. 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:  suprabasal keratinocyte (CL4033013)

 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 [suprabasal keratinocyte](/details-cell/CL4033013) is a differentiating epithelial cell located above the basal layer of the epidermis, characterized by the expression of markers such as keratin 1 and 10. The gene significance profile for this cell type reveals a highly specialized transcriptional landscape. **Overall**, its identity is uniquely defined by a remarkable number of antisense and long non-coding RNAs, such as `TBC1D8 AS1` and `KIAA2012 AS1`, suggesting that post-transcriptional regulation is a critical feature of this cell's differentiation state. Additionally, the high specificity of genes involved in oxidative stress response, such as [GPX4](/details-gene/2879), and the unexpected presence of an immune-related gene like [TRAV39](/details-gene/28642), point towards a specialized role in maintaining barrier integrity and potentially participating in local immune surveillance. ## Key Characteristics and Function Analysis of top marker genes, defined by expression specificity (`csi_z`), highlights several key functional themes for the [suprabasal keratinocyte](/details-cell/CL4033013). * **Transcriptional and Post-Transcriptional Regulation:** A dominant characteristic is the highly specific expression of numerous non-coding RNAs and uncharacterized transcripts. Genes such as [TBC1D8 AS1](/details-gene/100506286), [TMEM123 DT](/details-gene/101928424), [KIAA2012 AS1](/details-gene/729224), and [LINC02877](/details-gene/152118) are among the most specific markers. This pattern strongly suggests that a complex network of regulatory RNAs is essential for orchestrating the precise gene expression program required for keratinocyte differentiation and function in the suprabasal layer. The transcription factor [DBX2](/details-gene/440097) also shows high specificity, indicating its potential role in directing this unique transcriptional program. * **Oxidative Stress and Mitochondrial Dynamics:** The high significance of [GPX4](/details-gene/2879), a key enzyme that protects against lipid peroxidation and regulates ferroptotic cell death, indicates that these cells are equipped with specialized mechanisms to handle oxidative stress. This is consistent with their location in the epidermis, where they are exposed to environmental insults. Furthermore, the specific expression of [FIS1](/details-gene/51024), a protein involved in mitochondrial fission, suggests that dynamic control of mitochondrial morphology and function is important for this cell's physiology. * **Cell Adhesion and Structural Integrity:** The expression of genes involved in cell adhesion, such as [PCDHB15](/details-gene/56121) and [STRC](/details-gene/161497), is consistent with the cell's role in maintaining the structural cohesion of the epidermis. As these cells migrate upwards from the basal layer, stable cell-cell and cell-matrix interactions are crucial for barrier function. * **Anomalous Immune Gene Expression:** The high specificity of [TRAV39](/details-gene/28642), a T-cell receptor alpha variable gene, is highly unusual for a non-lymphoid cell. While its function in this context is unknown, it may suggest a novel role for keratinocytes in antigen recognition or immune modulation, a function that warrants further investigation. * **Anti-Markers:** The lack of specificity for ubiquitously expressed genes involved in core cellular processes such as mRNA splicing ([SNRPD2](/details-gene/6633)), protein degradation ([PSMB8](/details-gene/5696)), and fundamental metabolism ([SLC25A6](/details-gene/293), [NDUFB4](/details-gene/4710)) reinforces that the identity of the [suprabasal keratinocyte](/details-cell/CL4033013) is defined by its specialized functions rather than basal cellular machinery. The relatively low specificity of [SPRR2B](/details-gene/6701), a cornified envelope precursor, may indicate that its peak expression occurs at a later stage of differentiation, such as in the granular layer. ## Clinical Significance and Contextual Roles **Overall**, the gene signature of suprabasal keratinocytes provides insights into skin homeostasis and pathology. The prominent role of [GPX4](/details-gene/2879) positions these cells as critical regulators of ferroptosis in the skin. Dysregulation of this pathway is implicated in various inflammatory skin conditions, wound healing, and skin cancers, suggesting that suprabasal keratinocytes could be a key therapeutic target for diseases involving oxidative damage. The prion-related protein Doppel, encoded by [PRND](/details-gene/23627), shows high specificity in these cells. While primarily studied in the context of neurodegenerative diseases ([Link](https://doi.org/10.1006/jmbi.1999.3108)), its function in the epidermis is unknown but could relate to protein aggregation or cell signaling processes relevant to skin aging or disease. Mutations in [STRC](/details-gene/161497) are known to cause non-syndromic deafness and male infertility ([Link](https://doi.org/10.1136/jmg.2006.045765)), highlighting a potential shared molecular mechanism or developmental pathway between the inner ear and the skin. Its specific expression in keratinocytes may point to an uncharacterized role in epidermal adhesion or mechanosensing. ## Potential Mechanisms and Research Directions 1. **Hypothesis: Suprabasal keratinocyte differentiation is orchestrated by a unique network of non-coding RNAs that fine-tune gene expression to establish a specialized cellular state.** The landscape of top markers is dominated by antisense transcripts and lncRNAs, suggesting they are not merely byproducts of transcription but active regulators. * **Surprising Findings:** The most specific markers for this well-known cell type are not classic structural proteins like keratins, but rather a host of poorly understood non-coding RNAs. This indicates a significant gap in our understanding of the regulatory circuits governing epidermal stratification. * **Testable Questions:** Does the targeted knockdown of [TBC1D8 AS1](/details-gene/100506286) or [LINC02877](/details-gene/152118) in an organotypic human skin equivalent model disrupt normal stratification or alter the expression of key differentiation markers like KRT1, KRT10, and loricrin? 2. **Hypothesis: Suprabasal keratinocytes act as non-professional immune sentinels through the expression of unconventional immune-related genes.** The highly specific expression of the T-cell receptor component [TRAV39](/details-gene/28642) suggests a potential, non-canonical role in recognizing environmental or microbial antigens. This, combined with a specialized capacity to manage oxidative stress via [GPX4](/details-gene/2879), may allow these cells to initiate or modulate local immune responses. * **Surprising Findings:** The expression of a gene segment canonically restricted to T-lymphocytes within an epithelial cell challenges fundamental principles of cell lineage fidelity and suggests a previously unimagined functional plasticity for keratinocytes. * **Testable Questions:** Can a protein product of the [TRAV39](/details-gene/28642) gene be detected on the surface or within suprabasal keratinocytes using highly specific antibodies? If so, does its expression level or localization change upon exposure of skin models to common skin commensals or pathogens, such as *Staphylococcus aureus*?