Details for: CL0002279

Cell ID: CL0002279

Cell Name: type L enteroendocrine cell

Description: A enteroendocrine cell type that is numerous in ileum, present in jejunum and large intestine, few in duodenum. This cell type produces glucagon-like immunoreactants (glicentin, glucagon-37, glucagon-29, GLP-1 and -2) and PYY.

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

Significant Genes List

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

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Select a context for the target cell.
Target Cell for CSI:  type L enteroendocrine cell (CL0002279)

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Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
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 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 [type L enteroendocrine cell](/details-cell/CL0002279) is a specialized hormone-producing cell found predominantly in the ileum and large intestine. Its primary role involves the synthesis and secretion of key metabolic hormones, including glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), and peptide YY (PYY). The gene significance profile for this cell type is overwhelmingly dominated by genes involved in mitochondrial energy production. The high expression specificity of numerous mitochondrially-encoded genes, such as [COX2](/details-gene/4513) (CSI: 58.76) and [COX1](/details-gene/4512) (CSI: 56.25), suggests that the [type L enteroendocrine cell](/details-cell/CL0002279) operates at an exceptionally high metabolic rate, a characteristic likely essential for the energetically demanding process of peptide hormone synthesis and secretion. ## Key Characteristics and Function **Overall**, the molecular signature of the [type L enteroendocrine cell](/details-cell/CL0002279) points towards a highly specialized function as a metabolic sensor and hormone factory, defined by two principal functional clusters. * **Mitochondrial Bioenergetics:** The most striking feature of this cell is the profound significance of genes related to aerobic respiration. The top markers are almost exclusively components of the mitochondrial electron transport chain, including subunits of Complex IV ([COX2](/details-gene/4513), [COX1](/details-gene/4512), [COX6C](/details-gene/1345), [COX4I1](/details-gene/1327), [COX5B](/details-gene/1329)), Complex I ([ND4](/details-gene/4538), [ND3](/details-gene/4537), [ND2](/details-gene/4536), [ND1](/details-gene/4535), [ND5](/details-gene/4540)), Complex III ([CYTB](/details-gene/4519)), and Complex V ([ATP6](/details-gene/4508)). The high z-score based CSI values for these genes indicate their expression is uniquely pronounced in this cell type compared to others, establishing this extreme metabolic capacity as a core part of its identity. This is consistent with the immense ATP requirement for the synthesis, packaging, and regulated exocytosis of peptide hormones. * **Calcium-Dependent Secretory Machinery:** Supporting its endocrine function, the cell shows high significance for key calcium-binding proteins. [CALM1](/details-gene/801) (Calmodulin 1) and [S100A6](/details-gene/6277) (Calcyclin) are critical mediators of calcium signaling, a central process for triggering the exocytosis of hormone-containing granules. The high expression of [MYL6](/details-gene/4637), a myosin light chain, further suggests a well-developed actomyosin cytoskeleton, which is necessary for the transport and docking of secretory vesicles at the plasma membrane. The tumor protein [TPT1](/details-gene/7178), also involved in calcium binding, further reinforces this theme. The anti-marker profile helps to refine the cell's identity. The low significance of genes like [GPA33](/details-gene/10223), a marker for colonic epithelium, may suggest a distinct lineage or surface protein profile compared to absorptive enterocytes. Similarly, the lack of significance for the antigen-presenting gene [HLA-DPA1](/details-gene/3113) is consistent with a non-immunological role. ## Clinical Significance and Contextual Roles As producers of GLP-1, [type L enteroendocrine cells](/details-cell/CL0002279) are of major clinical importance, particularly in the context of type 2 diabetes and obesity. GLP-1 is an incretin hormone that potentiates insulin secretion, suppresses glucagon release, and promotes satiety. Consequently, GLP-1 receptor agonists are a cornerstone of modern diabetes and weight-loss therapies. The provided data, representing an **Overall** context, highlights the fundamental machinery required for this function. The cell's reliance on a vast mitochondrial network underscores its role as a key regulator of systemic energy homeostasis. While this dataset does not provide a comparative view of healthy versus diseased states, the genes identified here represent foundational pathways. Dysregulation of the energy production ([COX1](/details-gene/4512), [ND4](/details-gene/4538)) or calcium signaling ([CALM1](/details-gene/801)) pathways could plausibly lead to impaired hormone secretion, contributing to metabolic disorders. The differentiation of colonic adenocarcinoma cells has been linked to increased expression of mitochondrial RNA, including [ND4](/details-gene/4538) ([Link](https://pubmed.ncbi.nlm.nih.gov/1377597/)), suggesting that the metabolic state highlighted in these cells may also be relevant in intestinal cancers. ## Potential Mechanisms and Research Directions Based on the provided data, we can propose the following hypotheses for further investigation. 1. **Hypothesis: Type L cells are defined by a state of metabolic hyper-specialization, where mitochondrial machinery is uniquely upregulated beyond typical bioenergetic needs to directly fuel and regulate hormone secretion.** The extreme specificity (`csi_z`) of nearly every core component of the electron transport chain suggests this is not merely a "housekeeping" function but a central, defining feature of the cell's specialized identity. This metabolic state may be intrinsically linked to the cell's ability to sense nutrients and translate those signals into hormonal output. * **Surprising Findings:** It is highly unusual for ubiquitous, core metabolic genes like [COX1](/details-gene/4512) and [ND4](/details-gene/4538) to serve as top *specificity* markers. This implies that surrounding cell types in the gut have a comparatively low or different metabolic signature, making the [type L enteroendocrine cell](/details-cell/CL0002279) a distinct metabolic outlier rather than just another active cell. * **Testable Questions:** How does the secretagogue-induced release of GLP-1 and PYY correlate with real-time measurements of mitochondrial respiration (e.g., oxygen consumption rate) in isolated [type L enteroendocrine cells](/details-cell/CL0002279)? Does pharmacologic inhibition of Complex I or IV disproportionately affect hormone secretion compared to cell viability? 2. **Hypothesis: The calcium-binding protein [S100A6](/details-gene/6277) acts as a critical integrator of cellular metabolic status and calcium signaling to fine-tune hormone exocytosis.** While [CALM1](/details-gene/801) is a canonical mediator of calcium-dependent secretion, the high significance of [S100A6](/details-gene/6277), a protein also linked to cell proliferation and growth factor response ([Link](https://doi.org/10.1016/s0021-9258(18)67137-6)), suggests a more complex regulatory role. It may function to modulate the sensitivity of the secretory machinery to calcium influx based on the cell's energetic state or other microenvironmental cues. * **Surprising Findings:** The prominence of a "growth-regulated" gene like [S100A6](/details-gene/6277) in what is considered a post-mitotic, terminally differentiated cell type is unexpected. This may indicate a novel, non-proliferative function for this protein in the context of high-demand endocrine secretion, potentially linking cellular stress or nutrient availability to the secretory pathway. * **Testable Questions:** Does the knockdown of [S100A6](/details-gene/6277) in a [type L enteroendocrine cell](/details-cell/CL0002279) model alter the kinetics or magnitude of GLP-1 release in response to a calcium ionophore, even when initial calcium influx is unchanged? Does the expression or localization of [S100A6](/details-gene/6277) change in response to metabolic stressors like hypoxia or glucose deprivation?