Details for: CL0009038

Cell ID: CL0009038

Cell Name: colon macrophage

Description: This is a general grouping term created for use in the EMBL-EBI Single Cell Expression Atlas anatomograms. Please use a more specific cell type term for annotation if possible, given the information available to you.

Synonyms: macrophage of colon

Selected Context(s): Overall

Gene Significance Landscape

Display Options
Score:
Display
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 colon macrophage 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 colon macrophage. 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 colon macrophage. 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 colon macrophage. 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:  colon macrophage (CL0009038)

 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 [colon macrophage](/details-cell/CL0009038) is a myeloid cell type integral to the immune surveillance and homeostasis of the colonic mucosa. Based on its gene significance profile, this cell is characterized by a uniquely high expression of genes involved in iron sequestration and metabolism, such as [FTL](/details-gene/2512) and [FTH1](/details-gene/2495). This defining feature, coupled with a strong signature of high metabolic activity and antigen presentation, suggests that the [colon macrophage](/details-cell/CL0009038) is a specialized phagocyte adapted to manage the iron-rich and microbially-dense environment of the large intestine, playing a critical role in both tissue integrity and immune defense. ## Key Characteristics and Function **Overall**, the gene expression landscape of the [colon macrophage](/details-cell/CL0009038) points to a cell with a highly specialized and active functional profile, defined by several key biological themes. * **Iron Metabolism and Sequestration:** The most specific markers for this cell type are components of the ferritin complex, [FTL](/details-gene/2512) (CSI: 22.94) and [FTH1](/details-gene/2495) (CSI: 20.44). The high specificity of these genes suggests that iron handling is not merely a housekeeping function but a core, defining specialization. This is critical in the colon for sequestering iron to prevent its use by pathogenic bacteria and to mitigate oxidative damage from free iron. * **High Metabolic Activity:** A striking feature is the high specificity score of numerous mitochondrially-encoded genes essential for the electron transport chain, including [ND2](/details-gene/4536), [ND4](/details-gene/4538), [ND3](/details-gene/4537), [ND1](/details-gene/4535), and [ATP6](/details-gene/4508). This indicates a reliance on oxidative phosphorylation and a high-energy state, likely necessary to fuel continuous surveillance, phagocytosis, and other immunological functions in the demanding gut environment. * **Antigen Presentation and Immune Signaling:** The cell displays a robust signature for antigen presentation and immune activation. High specificity is observed for MHC class I components like [HLA E](/details-gene/3133) and [B2M](/details-gene/567), and the MHC class II gene [HLA DPA1](/details-gene/3113), confirming its role as an antigen-presenting cell. Furthermore, the expression of key signaling adaptors such as [TYROBP](/details-gene/7305) (DAP12) and [FCER1G](/details-gene/2207) indicates its capacity for activation through various immunoreceptors. * **Polyamine Metabolism and Cellular Stress Response:** The high CSI for [SAT1](/details-gene/6303) (CSI: 22.40), a rate-limiting enzyme in polyamine catabolism, and [OAZ1](/details-gene/4946) suggests a distinct regulation of polyamines, which are critical for cell growth, differentiation, and inflammation. Concurrently, the prominence of stress-response genes like [HERPUD1](/details-gene/9709), which is induced by endoplasmic reticulum stress, suggests these cells are equipped to handle the high protein synthesis and inflammatory signals characteristic of the gut mucosa. * **Negative Markers:** The provided anti-markers, such as [GAS2L3](/details-gene/283431) and [OLR1](/details-gene/4973), do not belong to a single coherent functional or lineage group. Their low significance primarily confirms that the top markers are indeed highly specific and reinforces the distinct myeloid identity of the [colon macrophage](/details-cell/CL0009038) without strongly excluding other specific lineages based on this limited list. ## Clinical Significance and Contextual Roles Although this analysis is based on a single **Overall** context, the specific gene signature of [colon macrophages](/details-cell/CL0009038) has significant implications for colonic health and disease. The profound emphasis on iron homeostasis, marked by [FTL](/details-gene/2512) and [FTH1](/details-gene/2495), is particularly relevant in inflammatory bowel disease (IBD) and colorectal cancer. Dysregulation of iron metabolism by macrophages can exacerbate inflammation through ferroptosis and the generation of reactive oxygen species, and can also influence the composition of the gut microbiota. Thus, these cells may represent a critical control point in the balance between homeostasis and pathology in the colon. The high metabolic state, evidenced by the suite of mitochondrial genes, suggests that metabolic reprogramming could be a key factor in their functional polarization during disease. A shift in their metabolic profile could determine whether these macrophages adopt a pro-inflammatory (M1-like) or an anti-inflammatory/tissue-repair (M2-like) phenotype, a pivotal process in the progression or resolution of colitis. The expression of [ITM2B](/details-gene/9445), a gene associated with amyloid formation in familial dementia ([Link](https://doi.org/10.1038/21637)), is a noteworthy finding. Its high specificity in [colon macrophages](/details-cell/CL0009038) may indicate a novel role in the clearance of protein aggregates or extracellular matrix remodeling within the gut, a function that could be relevant in chronic inflammatory conditions or fibrosis. Furthermore, the expression of immune signaling molecules like [TYROBP](/details-gene/7305) and [FCER1G](/details-gene/2207) highlights their capacity to be potent drivers of immune responses. These pathways are critical for clearing pathogens but can also contribute to tissue damage if dysregulated, positioning these cells as potential therapeutic targets for modulating colonic inflammation. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The highly specific expression of ferritin genes ([FTL](/details-gene/2512) and [FTH1](/details-gene/2495)) suggests that [colon macrophages](/details-cell/CL0009038) function as primary regulators of mucosal iron availability. This mechanism likely serves to limit iron for microbial growth (nutritional immunity) and prevent iron-catalyzed oxidative damage. In disease states like IBD, dysregulation of this function could lead to iron overload, promoting inflammation via ferroptosis and altering the gut microbiome. * **Surprising Findings:** The observation that iron management genes have higher specificity scores than many canonical immune function genes suggests that this metabolic role may be more central to the identity of [colon macrophages](/details-cell/CL0009038) than previously appreciated. * **Testable Questions:** Does the targeted deletion of [FTH1](/details-gene/2495) in intestinal macrophages alter susceptibility to chemically-induced colitis and lead to a distinct shift in the luminal microbial community in a mouse model? 2. **Hypothesis:** The unique co-expression of genes for polyamine catabolism ([SAT1](/details-gene/6303)) and high mitochondrial respiratory activity (e.g., [ND2](/details-gene/4536), [ND4](/details-gene/4538)) points to a specialized metabolic program. It is plausible that [colon macrophages](/details-cell/CL0009038) utilize polyamine catabolism to fuel oxidative phosphorylation, supporting their high energetic demands for constant immune surveillance and phagocytosis in a manner that maintains tissue homeostasis and avoids excessive inflammation. * **Surprising Findings:** The prominence of [SAT1](/details-gene/6303), an enzyme often associated with cellular stress and proliferation control, as a top-defining marker for a tissue-resident macrophage is unexpected. It suggests a unique integration of polyamine and energy metabolism pathways that is specific to the colonic niche. * **Testable Questions:** How does pharmacological inhibition of [SAT1](/details-gene/6303) affect the basal oxygen consumption rate and ATP production of primary human [colon macrophages](/details-cell/CL0009038) at rest and following phagocytic challenge?