Details for: CL4030026

Cell ID: CL4030026

Cell Name: BEST4+ enteroycte

Description: An enterocyte of the human intestine expressing bestrophin-4 (BEST4) calcium-activated ion channels.

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 BEST4+ enteroycte 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 BEST4+ enteroycte. 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 BEST4+ enteroycte. 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 BEST4+ enteroycte. 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:  BEST4+ enteroycte (CL4030026)

 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 [BEST4+ enteroycte](/details-cell/CL4030026) is a specialized intestinal epithelial cell defined by the expression of the bestrophin-4 calcium-activated ion channel. The gene significance profile for this cell type is overwhelmingly dominated by an exceptionally strong and specific expression signature of mitochondrially-encoded genes. **Overall**, this suggests that the primary and defining characteristic of the [BEST4+ enteroycte](/details-cell/CL4030026) is an extraordinarily high level of metabolic activity, likely dedicated to powering energy-intensive processes such as ion and fluid transport across the intestinal barrier. ## Key Characteristics and Function The functional identity of the [BEST4+ enteroycte](/details-cell/CL4030026) is strongly defined by several core biological themes, underscored by genes with uniquely high expression specificity (high `csi_z` scores). * **Mitochondrial Bioenergetics:** The most striking feature of this cell is the profound significance of genes encoded by the mitochondrial genome. The top markers include numerous core components of the electron transport chain and ATP synthesis machinery, such as NADH dehydrogenase subunits ([ND3](/details-gene/4537), [ND2](/details-gene/4536), [ND4](/details-gene/4538), [ND5](/details-gene/4540), [ND1](/details-gene/4535)), cytochrome b ([CYTB](/details-gene/4519)), cytochrome c oxidase subunits ([COX2](/details-gene/4513), [COX1](/details-gene/4512)), and an ATP synthase subunit ([ATP6](/details-gene/4508)). The high specificity scores for these genes indicate that an exceptional level of aerobic respiration is a defining feature of this cell, likely to meet the high energetic demands of its specialized functions. * **RNA Processing and Regulation:** A secondary theme is a high activity in post-transcriptional gene regulation. Significant markers include several heterogeneous nuclear ribonucleoproteins ([HNRNPA2B1](/details-gene/3181), [HNRNPU](/details-gene/3192)), RNA-binding proteins ([RBM39](/details-gene/9584)), and RNA helicases ([DDX5](/details-gene/1655)), which are all involved in mRNA splicing and processing. The high expression of the long non-coding RNA [NEAT1](/details-gene/283131), a key component of nuclear paraspeckles, further supports a role for complex gene regulation in maintaining this cell's specialized state. * **Signaling and Cytoskeletal Activity:** The expression of calcium-binding proteins like [S100A6](/details-gene/6277) and [TPT1](/details-gene/7178) is consistent with the cell's definition as expressing a calcium-activated ion channel (BEST4). Additionally, the significance of [YWHAZ](/details-gene/7534), a 14-3-3 family protein, points to its involvement in diverse signal transduction pathways. * **Cellular Lineage Definition:** The anti-marker profile helps to clarify the cell's identity. The lack of significant expression of genes like [HAPLN2](/details-gene/60484) (brain-specific), [DLL4](/details-gene/54567) (arterial endothelium), and [CCL25](/details-gene/6370) (thymus-expressed chemokine) confirms its distinct epithelial lineage, separate from neural, vascular, or primary immune cell types. ## Clinical Significance and Contextual Roles Given the singular focus of the **Overall** context, the clinical relevance of the [BEST4+ enteroycte](/details-cell/CL4030026) appears tightly linked to its extreme metabolic phenotype. The cell's profound reliance on mitochondrial respiration suggests it may be particularly vulnerable to metabolic stress, hypoxia, or mitochondrial dysfunction, which are pathogenic factors in inflammatory bowel disease (IBD) and colorectal cancer. The high expression of [ND4](/details-gene/4538), for instance, has been correlated with the differentiation of HT-29 human colonic adenocarcinoma cells, suggesting that the metabolic state of [BEST4+ enteroycte](/details-cell/CL4030026) cells might be linked to epithelial differentiation pathways that are dysregulated in cancer [Link](https://pubmed.ncbi.nlm.nih.gov/1377597/). Furthermore, the cell's active machinery for RNA processing, indicated by markers like [SON](/details-gene/6651) and [RBM39](/details-gene/9584), suggests that disruptions in pre-mRNA splicing could be a potential mechanism of disease in this cell type. As splicing dysregulation is an emerging hallmark of various cancers, the role of [BEST4+ enteroycte](/details-cell/CL4030026) in intestinal homeostasis and pathology warrants further investigation. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The extreme mitochondrial gene expression signature is a direct functional specialization to provide the immense ATP required to power BEST4-mediated ion transport, positioning these cells as critical regulators of intestinal fluid and electrolyte balance. * **Surprising Findings:** It is highly unusual for mitochondrially-encoded genes, rather than nuclear-encoded ones, to be the most specific markers of a cell type. This suggests not just an upregulation of mitochondrial pathways, but a massive expansion of the mitochondrial compartment itself, which becomes the most distinguishing feature of the cell. * **Testable Questions:** Does pharmacologic inhibition of the electron transport chain in intestinal organoids lead to a selective loss of function or viability in [BEST4+ enteroycte](/details-cell/CL4030026) cells compared to other enterocyte populations? 2. **Hypothesis:** Due to their exceptionally high metabolic rate, [BEST4+ enteroycte](/details-cell/CL4030026) cells act as metabolic sensors within the epithelial lining, capable of detecting and responding to fluctuations in luminal nutrients or oxygen levels (hypoxia) and subsequently signaling to adjacent epithelial or immune cells. * **Surprising Findings:** The dominant genetic signature is related to core metabolic machinery ([ND3](/details-gene/4537), [CYTB](/details-gene/4519)) rather than dedicated cell-surface nutrient or oxygen receptors. This implies that the sensing capability may be an intrinsic property of their metabolic flux, rather than a conventional receptor-mediated process. * **Testable Questions:** Using single-cell RNA sequencing, how does the transcriptional profile of [BEST4+ enteroycte](/details-cell/CL4030026) cells change in response to hypoxic stress or exposure to specific microbial metabolites (e.g., short-chain fatty acids) relative to neighboring BEST4-negative enterocytes?