Details for: CL1001131

Cell ID: CL1001131

Cell Name: vasa recta ascending limb cell

Description: A cell that is part of some vasa recta ascending limb.

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

Image representation

Depiction of vasa recta ascending limb cell
Courtesy of SwissBioPics

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for vasa recta ascending limb 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 vasa recta ascending limb 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 vasa recta ascending limb 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 vasa recta ascending limb 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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Target Cell for CSI:  vasa recta ascending limb cell (CL1001131)

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Nodes (Genes):
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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 **vasa recta ascending limb cell** is a specialized cell type forming part of the vasa recta, the capillary networks in the renal medulla responsible for maintaining the corticomedullary osmotic gradient. **Overall**, the gene significance profile of this cell is dominated by an exceptionally strong signature of high metabolic activity, particularly mitochondrial respiration, and a distinct capacity for immune interaction. The most specific marker, [ITM2B](/details-gene/9445), a gene primarily associated with familial dementias, suggests a unique and potentially uncharacterized role in protein processing or cell signaling within the renal microenvironment. This, combined with prominent markers for cytoskeletal structure and antigen presentation, portrays a cell that is both a metabolic workhorse and an active participant in tissue homeostasis and immune surveillance. ## Key Characteristics and Function Analysis of the most specific gene markers for the [vasa recta ascending limb cell](/details-cell/CL1001131) reveals several core functional clusters. * **Mitochondrial Respiration and High Energy Metabolism:** A striking feature of this cell is the high specificity score for numerous genes encoding components of the mitochondrial electron transport chain. These include NADH dehydrogenase subunits ([ND2](/details-gene/4536), [ND1](/details-gene/4535), [ND4](/details-gene/4538)) and cytochrome c oxidase subunits ([COX2](/details-gene/4513), [COX1](/details-gene/4512), [CYTB](/details-gene/4519)), as well as a key component of ATP synthase ([ATP6](/details-gene/4508)). This collective signature strongly indicates a profound reliance on oxidative phosphorylation to meet high energetic demands, likely related to active transport processes essential for the kidney's countercurrent exchange mechanism. The high specificity of the housekeeping gene [GAPDH](/details-gene/2597) further supports a high basal metabolic rate. * **Immune System Interface:** The cell displays highly specific expression of [HLA-E](/details-gene/3133) and its essential partner [B2M](/details-gene/567) (beta-2-microglobulin). [HLA-E](/details-gene/3133) is a non-classical MHC class I molecule that typically presents a restricted set of peptides to inhibitory receptors on NK cells and subsets of T cells. This suggests that [vasa recta ascending limb cells](/details-cell/CL1001131) are actively engaged in modulating local immune responses, possibly to prevent inappropriate inflammation in the physiologically harsh environment of the renal medulla. * **Cytoskeletal Dynamics and Calcium Signaling:** A prominent group of markers includes several myosin light chain genes ([MYL12A](/details-gene/10627), [MYL6](/details-gene/4637), [MYL12B](/details-gene/103910)), which are critical for regulating actomyosin contractility and maintaining cell shape. This is complemented by other calcium-binding proteins like [TPT1](/details-gene/7178) and [S100A6](/details-gene/6277), indicating that calcium-dependent signaling pathways are central to the cell's function, likely controlling cytoskeletal organization and transport processes. * **Protein Processing and Metabolism:** The top marker, [ITM2B](/details-gene/9445), is involved in Golgi membrane protein processing. Its presence, along with [SRP14](/details-gene/6727) (a component of the signal recognition particle), points to significant activity in protein synthesis and trafficking. Furthermore, the high specificity of [FTH1](/details-gene/2495) suggests a crucial role in iron sequestration, which is vital for managing oxidative stress in a metabolically active cell. * **Defining by Exclusion (Anti-Markers):** The low significance scores for genes typically associated with active angiogenesis ([EPHB4](/details-gene/2050), [ROBO4](/details-gene/54538), [RASIP1](/details-gene/54922)), strong extracellular matrix deposition ([COL3A1](/details-gene/1281)), and potent chemokine-mediated immune cell recruitment ([CCL2](/details-gene/6347)) suggest that under baseline conditions, these cells are terminally differentiated and not primary drivers of vascular remodeling or acute inflammatory infiltration. ## Clinical Significance and Contextual Roles The gene profile of the [vasa recta ascending limb cell](/details-cell/CL1001131) highlights its potential involvement in several pathological processes. The most notable clinical connection is through [ITM2B](/details-gene/9445). Mutations in this gene are known to cause familial British dementia and familial Danish dementia by producing amyloidogenic peptides [Link](https://doi.org/10.1038/21637). Its extreme specificity in this renal cell type is unexpected and raises questions about a potential, unappreciated link between kidney function and systemic amyloid precursor protein processing, or a distinct, non-pathological role for [ITM2B](/details-gene/9445) in the kidney. The pronounced dependence on mitochondrial function makes this cell type a potential target in mitochondrial diseases or conditions causing renal hypoxia, such as ischemic acute kidney injury. The specific expression of numerous mitochondrially-encoded genes ([ND1](/details-gene/4535), [ND2](/details-gene/4536), [COX1](/details-gene/4512), etc.) suggests that mutations in mitochondrial DNA could disproportionately affect the function of the vasa recta, leading to impaired urinary concentration. Furthermore, the strong expression of the [HLA-E](/details-gene/3133)/[B2M](/details-gene/567) complex positions this cell as a key player in renal immune surveillance. In the context of kidney transplantation, variations in [HLA-E](/details-gene/3133) could influence allograft rejection by modulating NK cell activity. In autoimmune diseases like lupus nephritis, dysregulation of this immune-inhibitory pathway could contribute to tissue damage. The expression of [HMGB1](/details-gene/3146), a known damage-associated molecular pattern (DAMP), further implicates these cells in the initiation of sterile inflammation following injury. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The [vasa recta ascending limb cell](/details-cell/CL1001131) utilizes [ITM2B](/details-gene/9445) as a specialized regulator of membrane protein turnover or signaling, essential for managing the unique transport and osmotic stress conditions of the renal medulla. Its function here is unrelated to amyloidogenesis but is instead a specific adaptation for renal physiology. * **Surprising Finding:** The most defining marker of a specialized kidney cell is a gene whose known pathology is exclusively neurological, suggesting a novel, context-dependent function. * **Testable Question:** Does targeted deletion of [ITM2B](/details-gene/9445) in the renal tubular epithelium of a mouse model alter the expression or localization of key ion and water channels (e.g., aquaporins, urea transporters) in the vasa recta, and does it impair the animal's ability to concentrate urine under water-deprivation stress? 2. **Hypothesis:** The constitutive high-level expression of the [HLA-E](/details-gene/3133)/[B2M](/details-gene/567) complex serves as a primary mechanism to establish an immune-privileged state within the renal medulla, protecting these metabolically active and potentially vulnerable cells from cytotoxic NK cell-mediated damage. * **Surprising Finding:** A non-lymphoid structural cell exhibits a marker profile more akin to a cell actively managing immune tolerance, suggesting it is under constant surveillance and must proactively inhibit cytotoxic responses. * **Testable Question:** In an in-vitro co-culture system, do [vasa recta ascending limb cells](/details-cell/CL1001131) inhibit the activation and degranulation of primary human NK cells, and is this inhibition reversed by blocking the interaction between [HLA-E](/details-gene/3133) and its cognate inhibitory receptor NKG2A on NK cells?