Details for: CL0000164

Cell ID: CL0000164

Cell Name: enteroendocrine cell

Description: An endocrine cell that is located in the epithelium of the gastrointestinal tract or in the pancreas.

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 enteroendocrine 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 enteroendocrine 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 enteroendocrine 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 enteroendocrine 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:  enteroendocrine cell (CL0000164)

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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 [enteroendocrine cell](/details-cell/CL0000164) is a specialized endocrine cell located within the epithelium of the gastrointestinal tract and pancreas. Analysis of its gene significance profile in the **Overall** context reveals a striking and defining characteristic: an exceptionally high and specific expression of genes related to mitochondrial bioenergetics. The top markers are overwhelmingly components of the electron transport chain, such as [COX1](/details-gene/4512) (CSI: 73.19), [ND4](/details-gene/4538) (CSI: 71.77), and [COX2](/details-gene/4513) (CSI: 71.10). This signature strongly suggests that the core identity of this cell type is intrinsically linked to a massive capacity for aerobic respiration, likely to fuel its primary function of hormone synthesis and secretion. ## Key Characteristics and Function The gene expression profile of the [enteroendocrine cell](/details-cell/CL0000164) is dominated by several key functional clusters that define its role as a high-energy metabolic and secretory hub. * **Mitochondrial Bioenergetics and Oxidative Phosphorylation:** This is the most prominent functional signature of the [enteroendocrine cell](/details-cell/CL0000164). An extensive list of top markers with exceptionally high specificity scores (`csi_z`) are components of the mitochondrial respiratory chain. This includes mitochondrially-encoded genes like [COX1](/details-gene/4512), [ND4](/details-gene/4538), [COX2](/details-gene/4513), [CYTB](/details-gene/4519), and [ND2](/details-gene/4536), as well as nuclear-encoded subunits such as [COX4I1](/details-gene/1327), [COX7C](/details-gene/1350), [COX7A2](/details-gene/1347), and [COX5B](/details-gene/1329). In addition, key components of the ATP synthase complex, including [ATP5MG](/details-gene/10632), [ATP5F1E](/details-gene/514), and [ATP5MC2](/details-gene/517), are also highly specific markers. This profound enrichment indicates that these cells possess a massive capacity for ATP production through oxidative phosphorylation, a feature essential for the energy-intensive processes of synthesizing, packaging, and secreting hormones. * **Iron Homeostasis:** Tightly linked to its metabolic profile, the cell shows highly specific expression of ferritin heavy and light chain genes, [FTH1](/details-gene/2495) and [FTL](/details-gene/2512). Ferritin is the primary intracellular iron storage protein, and its abundance is crucial for sequestering iron in a non-toxic form. This is particularly important in a cell with high mitochondrial activity, as iron is a critical component of heme groups and iron-sulfur clusters within the electron transport chain, but can also catalyze the formation of reactive oxygen species. This suggests a sophisticated system for managing iron to support energy production while mitigating oxidative stress. * **General Cellular Machinery and Cytoskeletal Dynamics:** Several highly-ranked genes point to robust housekeeping and structural functions necessary for a secretory cell. These include the histone variants [H3 3A](/details-gene/3020) and [H3 3B](/details-gene/3021), the ubiquitin gene [UBB](/details-gene/7314), and the actin-binding protein [CFL1](/details-gene/1072). High expression of histone variants and ubiquitin may reflect active transcription and high protein turnover, while cofilin's role in actin dynamics is consistent with the cytoskeletal rearrangements required for vesicle transport and exocytosis. **Overall**, the anti-marker profile is also informative. The relatively low specificity score for the motilin gene ([MLN](/details-gene/4295)) is notable. Given that motilin is produced by a specific subset of [enteroendocrine cells](/details-cell/CL0000164), its lack of prominence as a general marker suggests that this analysis captures a heterogeneous population where no single hormone product defines the entire class. Instead, the underlying metabolic machinery appears to be the most universal and defining feature. ## Clinical Significance and Contextual Roles The dominant bioenergetic profile of [enteroendocrine cells](/details-cell/CL0000164) places them at the center of gut metabolism and highlights their potential vulnerability in metabolic diseases. Their immense reliance on oxidative phosphorylation suggests that mitochondrial dysfunction could severely impair their ability to sense nutrients and secrete critical hormones like GLP-1, GIP, and serotonin, which regulate systemic glucose homeostasis, appetite, and gut motility. The connection between mitochondrial gene expression and cellular state is underscored by research on [ND4](/details-gene/4538), where its increased expression was found to correlate with the differentiation of HT-29 human colonic adenocarcinoma cells ([Link](https://pubmed.ncbi.nlm.nih.gov/1377597/)). This suggests that the metabolic phenotype identified here may not only be a feature of normal function but could also be modulated during pathological processes like tumorigenesis, potentially serving as a biomarker for cellular differentiation status in colon cancer. Furthermore, the prominent iron management signature, represented by [FTH1](/details-gene/2495) and [FTL](/details-gene/2512), indicates a potential role for these cells in local iron handling within the gut mucosa. Dysregulation of this function could contribute to pathologies associated with either iron deficiency or overload, and could influence the local inflammatory environment, as ferritin levels are often modulated during immune responses. ## Potential Mechanisms and Research Directions 1. **Hypothesis: The high-capacity bioenergetic machinery of [enteroendocrine cells](/details-cell/CL0000164) serves as the primary sensor and integrator of luminal nutrient status, directly coupling metabolic flux to hormone secretion profiles.** The cell's identity appears to be defined more by its metabolic engine than its secretory products, suggesting that the rate of oxidative phosphorylation itself might be the critical regulatory node that determines the pattern and quantity of hormone release in response to different nutrients (e.g., glucose vs. fatty acids). * **Surprising Findings:** The most specific genetic markers for this diverse class of secretory cells are not the hormones they are known for (e.g., [MLN](/details-gene/4295)), but rather the ubiquitous mitochondrial components that power their function. This implies that the metabolic *potential* is a more fundamental and universal identifier for the lineage than any single endocrine output. * **Testable Questions:** How do specific inhibitors of different electron transport chain complexes (e.g., rotenone for Complex I, antimycin A for Complex III) alter the secretory response of primary [enteroendocrine cells](/details-cell/CL0000164) to glucose, short-chain fatty acids, and amino acids? Does this inhibition affect the secretion of all hormones equally, or are certain endocrine pathways more sensitive to disruptions in specific parts of the respiratory chain? 2. **Hypothesis: The pronounced expression of ferritin ([FTH1](/details-gene/2495)/[FTL](/details-gene/2512)) indicates that [enteroendocrine cells](/details-cell/CL0000164) function as critical iron-buffering hubs within the intestinal crypt, protecting both themselves and neighboring stem cells from iron-induced oxidative stress generated by high metabolic activity.** This secondary role in iron homeostasis may be essential for maintaining the integrity and regenerative capacity of the gut epithelium. * **Surprising Findings:** A cell type primarily characterized by its endocrine function demonstrates a gene-specificity signature for iron storage ([FTH1](/details-gene/2495) CSI: 70.70) that is nearly on par with its top mitochondrial markers. This suggests iron management is not merely a supportive function but a co-defining characteristic of the cell. * **Testable Questions:** Does conditional knockout of [FTH1](/details-gene/2495) specifically in [enteroendocrine cells](/details-cell/CL0000164) lead to increased markers of oxidative stress (e.g., lipid peroxidation) and reduced cell viability under high-energy-demand conditions? Furthermore, does this knockout affect the proliferation or differentiation rates of adjacent Lgr5-positive intestinal stem cells, particularly in models of high dietary iron?