Details for: CL0000091

Cell ID: CL0000091

Cell Name: Kupffer cell

Description: Markers: Mouse: F4/80+, CD11b-low, CD68+, sialoadhesin+, CD163/SRCR+; role or process: immune, antigen-presentation, clearance of senescent erythrocytes, iron metabolism. Kupffer cells are also reportedly C3aR-positive, CD14-low, CD54-positive, CD88-positive, and CD284-positive. They are also capable of producing IL-1, IL-6, TNF-alpha, nitric oxide, PGD2, PGE2, PGF2alpha, and TXA2.

Synonyms: hepatic macrophage, littoral cell of hepatic sinusoid, liver macrophage, macrophagocytus stellatus, stellate cell of von Kupffer, von Kupffer cell

Selected Context(s): Overall

Gene Significance Landscape

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

Image representation

Depiction of Kupffer cell
Courtesy of SwissBioPics

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for Kupffer 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 Kupffer 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 Kupffer 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 Kupffer 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.

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Target Cell for CSI:  Kupffer cell (CL0000091)

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Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
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 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 [Kupffer cell](/details-cell/CL0000091) is a specialized, liver-resident macrophage critical for immune surveillance, antigen presentation, and metabolic homeostasis within the hepatic sinusoid. Based on its gene significance profile, this cell type is characterized by exceptionally active metabolic pathways, particularly those related to polyamine and iron metabolism. The high specificity scores for genes like [SAT1](/details-gene/6303), [FTL](/details-gene/2512), and [FTH1](/details-gene/2495) underscore its primary roles in clearing senescent erythrocytes, managing systemic iron levels, and maintaining a high state of metabolic readiness essential for its phagocytic and immune functions. ## Key Characteristics and Function **Overall**, the gene expression landscape of the [Kupffer cell](/details-cell/CL0000091) points to a highly specialized cell with distinct metabolic and immune functions. The top markers can be grouped into several key functional clusters: * **Polyamine Metabolism:** The most specific marker is [SAT1](/details-gene/6303) (spermidine/spermine N1-acetyltransferase), a rate-limiting enzyme in polyamine catabolism. Its high CSI score, complemented by the significant expression of [OAZ1](/details-gene/4946) (ornithine decarboxylase antizyme), suggests that precise regulation of intracellular polyamine levels is a core, identifying feature of this cell. Polyamines are crucial for cell proliferation and inflammatory responses, indicating this pathway may be central to modulating Kupffer cell activation. * **Iron Homeostasis:** The prominent specificity of ferritin light chain ([FTL](/details-gene/2512)) and heavy chain ([FTH1](/details-gene/2495)) is fully consistent with the Kupffer cell's well-established role in processing iron from senescent red blood cells. These proteins are essential for safely sequestering iron, preventing oxidative stress within the liver microenvironment. * **Macrophage Lineage and Antigen Presentation:** The high significance of [SPI1](/details-gene/6688) (PU.1), a master transcription factor for myeloid development, firmly establishes its identity as a macrophage. Furthermore, the high expression specificity of [B2M](/details-gene/567) (Beta-2-microglobulin), a required component of MHC class I molecules, directly supports its described function in antigen presentation to other immune cells. * **High Metabolic and Bioenergetic Activity:** A large number of top markers are components of the mitochondrial respiratory chain and ATP synthesis machinery, including [COX5B](/details-gene/1329), [COX4I1](/details-gene/1327), [COX1](/details-gene/4512), [ATP5F1E](/details-gene/514), and [UQCRB](/details-gene/7381). This collective signature points to a high demand for ATP, likely fueling energy-intensive processes such as phagocytosis, protein synthesis, and maintaining ionic gradients via pumps like [ATP1B1](/details-gene/481). * **Transcriptional and Translational Regulation:** The significance of genes like [PABPC1](/details-gene/26986) and the long non-coding RNA [NEAT1](/details-gene/283131) suggests sophisticated control over gene expression at both post-transcriptional and nuclear organization levels, enabling rapid responses to environmental cues. The anti-marker profile further refines the cell's identity. The lack of specificity for genes like [KRT8](/details-gene/KRT8) confirms its non-epithelial origin. The negative CSI for multiple heterogeneous nuclear ribonucleoproteins (e.g., [HNRNPDL](/details-gene/9987), [HNRNPA1](/details-gene/3178)) and chromatin-associated proteins like [HMGB1](/details-gene/3146) may indicate a unique nuclear architecture or a specialized set of RNA-binding proteins compared to other cell types in the dataset. ## Clinical Significance and Contextual Roles **Overall**, the unique gene signature of [Kupffer cells](/details-cell/CL0000091) positions them as central players in liver health and disease. The profound enrichment for iron-handling machinery ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)) implicates these cells directly in pathologies of iron overload, such as hemochromatosis, where their capacity to store iron can be overwhelmed, leading to hepatic injury. Conversely, their role in iron recycling is vital for erythropoiesis, and dysfunction could contribute to certain anemias. The high specificity of the transcription factor [KLF6](/details-gene/1316), previously shown to be up-regulated in early hepatic fibrosis ([Link](https://pubmed.ncbi.nlm.nih.gov/9689109/)), strongly suggests that [Kupffer cells](/details-cell/CL0000091) are early responders and potential drivers of the fibrotic process in the liver. Their activation and subsequent release of pro-inflammatory and pro-fibrotic mediators are key events in the progression of liver diseases like non-alcoholic steatohepatitis (NASH) and alcoholic liver disease. The top marker, [SAT1](/details-gene/6303), and its associated polyamine pathway have been linked to inflammation and cell growth. Dysregulation of this pathway in [Kupffer cells](/details-cell/CL0000091) could therefore be a critical factor in both chronic liver inflammation and the development of hepatocellular carcinoma, where these cells form a major component of the tumor microenvironment. Similarly, [GSTP1](/details-gene/2950), a key detoxification enzyme, highlights the cell's role in protecting the liver from xenobiotics and oxidative stress, a function that can be compromised in toxic liver injury. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** Given the exceptional specificity score of [SAT1](/details-gene/6303), we hypothesize that polyamine catabolism is not just a housekeeping function but a primary regulatory hub in [Kupffer cells](/details-cell/CL0000091). This pathway may act as a rheostat, controlling the switch between pro-inflammatory (M1-like) and pro-resolving (M2-like) phenotypes in response to liver damage or infection. * **Surprising Findings:** The emergence of a metabolic enzyme, [SAT1](/details-gene/6303), as the single most specific gene marker is unexpected, surpassing even classical macrophage surface receptors or transcription factors. This suggests its role in defining Kupffer cell identity is underappreciated. * **Testable Questions:** How does pharmacological or genetic inhibition of [SAT1](/details-gene/6303) alter the cytokine secretion profile and phagocytic capacity of [Kupffer cells](/details-cell/CL0000091) in response to stimulation with LPS or damaged hepatocytes? 2. **Hypothesis:** The concurrent high specificity of genes for iron storage ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)) and numerous mitochondrial respiratory chain subunits suggests a specialized functional coupling. We propose that iron acquired through erythrophagocytosis is preferentially utilized for the synthesis of iron-sulfur clusters and hemes for mitochondrial complexes, directly fueling the high energetic demands of phagocytosis and immune activation. * **Surprising Findings:** While high metabolic activity is expected, the data indicates a specific signature of mitochondrial components are enriched ([COX5B](/details-gene/1329), [ATP5F1E](/details-gene/514)), while others are anti-markers ([COX3](/details-gene/4514), [ATP6](/details-gene/4508)). This pattern may point towards a unique, adapted composition of respiratory supercomplexes in [Kupffer cells](/details-cell/CL0000091). * **Testable Questions:** Using isotopic tracing, can we demonstrate a preferential flux of iron derived from phagocytosed erythrocytes directly into mitochondrial heme and iron-sulfur cluster synthesis within [Kupffer cells](/details-cell/CL0000091), and does this flux increase upon immune stimulation?