Details for: CL0002268

Cell ID: CL0002268

Cell Name: P/D1 enteroendocrine cell

Description: An enteroendocrine cell that stores and secretes Ghrelin.

Selected Context(s): Overall

Gene Significance Landscape

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Score:
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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 P/D1 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 P/D1 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 P/D1 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 P/D1 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:  P/D1 enteroendocrine cell (CL0002268)

 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 [P/D1 enteroendocrine cell](/details-cell/CL0002268) is a specialized hormone-secreting cell, primarily defined by its role in producing and releasing Ghrelin. Based on its gene significance profile, this cell is characterized by an exceptionally high level of metabolic activity and a sophisticated machinery for protein synthesis and regulated secretion. The **Overall** analysis reveals that the most specific markers for this cell type are not necessarily hormone-related genes themselves, but rather a large suite of genes encoding components of the mitochondrial respiratory chain. This suggests that its identity is inextricably linked to its function as a high-energy bioenergetic hub, likely required to fuel the constant synthesis and pulsatile release of peptide hormones into circulation. ## Key Characteristics and Function Analysis of top marker genes, ranked by expression specificity (CSI Z-Score), highlights several core functional clusters that define the [P/D1 enteroendocrine cell](/details-cell/CL0002268). * **Bioenergetic Powerhouse:** A striking feature of this cell is the remarkable enrichment of genes involved in mitochondrial oxidative phosphorylation. Numerous subunits of the electron transport chain, including [COX1](/details-gene/4512), [ND4](/details-gene/4538), [COX2](/details-gene/4513), [ND2](/details-gene/4536), [ND3](/details-gene/4537), [ATP6](/details-gene/4508), [CYTB](/details-gene/4519), and [ND1](/details-gene/4535), are among the most specific markers. This profound signature indicates a massive energy demand, consistent with the high metabolic cost of synthesizing, packaging, and secreting large quantities of the peptide hormone Ghrelin. * **Regulated Secretory Pathway:** The cell's function in hormone secretion is underscored by the high specificity of genes integral to protein processing and calcium signaling. * **Protein Synthesis and Export:** High expression specificity of [SRP14](/details-gene/6727), a component of the signal recognition particle, points to a highly active pathway for co-translational translocation of secreted proteins into the endoplasmic reticulum. This is complemented by the high significance of genes involved in protein quality control and turnover, such as [SKP1](/details-gene/6500) and [UBB](/details-gene/7314). * **Calcium-Mediated Exocytosis:** A sophisticated calcium signaling apparatus is suggested by the high scores for multiple calcium-binding proteins, including [CALM2](/details-gene/805), [CALM1](/details-gene/801), and [S100A6](/details-gene/6277). This indicates that calcium is a critical second messenger for regulated exocytosis. Furthermore, the high specificity of [SARAF](/details-gene/51669), a negative regulator of store-operated calcium entry, suggests the presence of a robust feedback mechanism to precisely control intracellular calcium levels and prevent cellular stress from excessive calcium influx during secretory events ([Link](https://doi.org/10.1016/j.cell.2012.01.055)). The list of anti-markers helps to refine the cell's identity. The low significance of genes like [SCT](/details-gene/6343) (Secretin) and [FFAR4](/details-gene/338557) (a free fatty acid receptor) distinguishes it from other enteroendocrine lineages, confirming its specialized function. ## Clinical Significance and Contextual Roles While the provided analysis does not compare different biological states, the unique gene signature of the [P/D1 enteroendocrine cell](/details-cell/CL0002268) has potential clinical implications, particularly concerning metabolism and neurodegeneration. * **Metabolic Regulation:** As the primary source of Ghrelin, the "hunger hormone," this cell is a central player in appetite regulation and energy homeostasis. Its extreme reliance on mitochondrial function suggests that therapeutic strategies targeting cellular metabolism could modulate Ghrelin output, with potential applications in obesity, cachexia, and metabolic syndrome. * **Potential Role in Neurodegeneration:** A highly intriguing and specific marker for this cell is [ITM2B](/details-gene/9445). Mutations in [ITM2B](/details-gene/9445) are known to cause familial British and Danish dementias, which are characterized by cerebral amyloid deposits ([Link](https://doi.org/10.1038/21637), [Link](https://doi.org/10.1073/pnas.080076097)). The specific and high-level expression of this amyloid-associated gene in a gut endocrine cell is unexpected and may suggest a novel link between gastrointestinal hormone-producing cells and the pathophysiology of neurodegenerative diseases, possibly via a gut-brain signaling axis. * **Immune System Interaction:** The high specificity of [B2M](/details-gene/567), a key component of MHC class I molecules, is notable. While expressed by most cells, its prominence as a marker here may suggest a high rate of protein turnover and peptide presentation, potentially implicating the [P/D1 enteroendocrine cell](/details-cell/CL0002268) in interactions with the local immune system in the gut mucosa. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The extreme enrichment of mitochondrial respiratory chain genes indicates that the bioenergetic capacity of [P/D1 enteroendocrine cells](/details-cell/CL0002268) is a primary determinant of their function and may represent a rate-limiting factor in Ghrelin production. * **Surprising Findings:** It is remarkable that the most specific genetic markers of this cell are not the hormone it produces, but rather the machinery that powers its production. This suggests that its metabolic phenotype is a more unique identifier than its endocrine product, distinguishing it even from other hormone-secreting cells. * **Testable Questions:** Does pharmacological inhibition of mitochondrial complex I (e.g., using metformin or rotenone) disproportionately reduce Ghrelin secretion from primary gastric organoids compared to the secretion of other gut hormones like GLP-1 or Somatostatin? 2. **Hypothesis:** The specific, high-level expression of the dementia-associated gene [ITM2B](/details-gene/9445) in [P/D1 enteroendocrine cells](/details-cell/CL0002268) suggests a previously unrecognized role for this cell in producing and potentially secreting [ITM2B](/details-gene/9445)-derived peptides that could contribute to systemic amyloid biology or a gut-brain signaling axis relevant to neurodegeneration. * **Surprising Findings:** The discovery of a key gene for a familial amyloid-based dementia as a top specific marker for a gut hormone cell is highly unexpected. This finding challenges the brain-centric view of such pathologies and suggests a potential peripheral source for amyloidogenic peptides or related signaling molecules. * **Testable Questions:** Using mass spectrometry, can [ITM2B](/details-gene/9445)-derived peptides, such as ABri, be detected in the secretome of cultured [P/D1 enteroendocrine cells](/details-cell/CL0002268) or in the portal circulation of animal models under different metabolic conditions (e.g., fasting vs. fed)?