Details for: CL1001106

Cell ID: CL1001106

Cell Name: kidney loop of Henle thick ascending limb epithelial cell

Description: An epithelial cell that is part of some loop of Henle thick ascending limb. It is known in some mammalian species that this cell may express the Na+-K+-2Cl− cotransporter (NKCC2) apically.

Selected Context(s): Overall

Gene Significance Landscape

Display Options
Score:
Display
Genes

Contexts:

Cell Significance Index (CSI) is uniquely calculated to reveal cell-specific gene markers. More info here

Image representation

Depiction of kidney loop of Henle thick ascending limb epithelial cell
Courtesy of SwissBioPics

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for kidney loop of Henle thick ascending limb epithelial 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 kidney loop of Henle thick ascending limb epithelial 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 kidney loop of Henle thick ascending limb epithelial 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 kidney loop of Henle thick ascending limb epithelial 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:  kidney loop of Henle thick ascending limb epithelial cell (CL1001106)

 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.

Loading network (please wait)...

## Summary The [kidney loop of Henle thick ascending limb epithelial cell](/details-cell/CL1001106) is a highly specialized cell type critical for renal function. Its primary role, as indicated by its gene significance profile, is the energy-intensive active transport of ions, which is essential for creating the concentration gradient required for urine concentration. The cell is characterized by an exceptionally high expression of nuclear-encoded mitochondrial genes involved in aerobic respiration, such as [LDHB](/details-gene/3945) and [ATP5F1B](/details-gene/506), underscoring its massive ATP demand. This metabolic specialization is complemented by the expression of key ion transporters and channels, defining its role as a powerful engine for renal solute reabsorption. ## Key Characteristics and Function **Overall**, the gene expression landscape of the thick ascending limb (TAL) epithelial cell is dominated by genes underpinning a high-capacity energy production system, consistent with its physiological function. * **High Metabolic Activity and ATP Synthesis:** The most prominent feature of this cell is its profound investment in aerobic respiration. A large cluster of top marker genes are components of the electron transport chain and ATP synthase complex. These include subunits of Complex I ([NDUFA4](/details-gene/4697)), Complex III ([UQCRB](/details-gene/7381)), Complex IV ([COX4I1](/details-gene/1327), [COX5B](/details-gene/1329), [COX7C](/details-gene/1350)), and ATP synthase ([ATP5F1B](/details-gene/506), [ATP5PF](/details-gene/522), [ATP5MG](/details-gene/10632)). The high significance of [LDHB](/details-gene/3945) further suggests a high rate of lactate metabolism to fuel oxidative phosphorylation. This metabolic machinery is necessary to power the massive amount of active transport performed by these cells. * **Ion Transport and Membrane Potential Regulation:** The cell's primary physiological purpose is reflected in the high significance of genes directly involved in ion transport. [ATP1B1](/details-gene/481), the beta subunit of the Na+/K+-ATPase pump, is a key marker. The expression of the large-conductance calcium-activated potassium channel [KCNMA1](/details-gene/3778) is also highly specific, suggesting a critical role in maintaining the membrane potential necessary for ion transport and cellular homeostasis. * **Stress Response and Cytoskeletal Integrity:** The cell expresses markers associated with cellular stress and structural maintenance. [GSTP1](/details-gene/2950) is involved in detoxification and response to oxidative stress, a likely byproduct of high mitochondrial activity. Myosin light chains [MYL6](/details-gene/4637) and [MYL12B](/details-gene/103910) indicate an active cytoskeleton, which is crucial for maintaining cell polarity, shape, and the trafficking of transporters to the cell membrane. The calcium-binding protein [S100A6](/details-gene/6277) points towards a role for calcium signaling in regulating these processes. * **Novel Signaling and Adhesion Molecules:** Intriguingly, several top markers are typically associated with the nervous system. The high specificity of [NRG3](/details-gene/10718) (Neuregulin 3), [NLGN1](/details-gene/22871) (Neuroligin 1), and [PPFIA2](/details-gene/8499) suggests these molecules may have been co-opted for non-canonical roles in cell-cell communication or adhesion within the highly organized TAL epithelium. * **Defining Anti-Markers:** The anti-marker profile is particularly informative. There is a striking negative significance for multiple mitochondrial DNA-encoded genes, including subunits of Complex I ([ND1](/details-gene/4535), [ND2](/details-gene/4536), [ND3](/details-gene/4537), [ND4](/details-gene/4538)), Complex IV ([COX1](/details-gene/4512), [COX2](/details--gene/4513), [COX3](/details-gene/4514)), and Complex V ([ATP6](/details-gene/4508)). This contrasts sharply with the positive signature of nuclear-encoded mitochondrial genes and suggests a unique regulation of mitochondrial biogenesis or stoichiometry. Furthermore, the negative CSI for the ubiquitous glycolytic enzyme [GAPDH](/details-gene/2597) and immediate-early transcription factor [FOS](/details-gene/2353) indicates a highly specialized metabolic profile and a quiescent transcriptional state under baseline conditions. ## Clinical Significance and Contextual Roles Given that the TAL is a major site of oxygen consumption in the kidney, these cells are particularly vulnerable to ischemic injury, a common feature of acute kidney injury (AKI). The profound reliance on a specific suite of nuclear-encoded mitochondrial proteins suggests that genetic or acquired defects in these components could predispose individuals to kidney dysfunction. The unexpected expression of neuronal-associated genes like [NLGN1](/details-gene/22871) and [NRG3](/details-gene/10718) may open new avenues for understanding diseases affecting epithelial barrier integrity. Disruption of these putative cell-cell communication or adhesion pathways could contribute to the pathophysiology of tubulointerstitial diseases. Additionally, the presence of [ITM2B](/details-gene/9445), a gene linked to familial British and Danish dementia, is intriguing and its function in the kidney remains to be elucidated. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The [kidney loop of Henle thick ascending limb epithelial cell](/details-cell/CL1001106) employs a specialized strategy of mitochondrial biogenesis, favoring the expression of specific nuclear-encoded respiratory complex subunits over mitochondrial-encoded ones. This may create a unique stoichiometry within respiratory complexes, optimizing them for the sustained, high-level ATP production required for massive ion transport while potentially minimizing the production of reactive oxygen species. * **Surprising Findings:** The stark dichotomy between the high significance of nuclear-encoded mitochondrial protein genes (e.g., [COX4I1](/details-gene/1327), [ATP5F1B](/details-gene/506)) and the negative significance of mitochondrial DNA-encoded genes (e.g., [COX1](/details-gene/4512), [ND1](/details-gene/4535)) is highly unusual, as these proteins must co-assemble into functional complexes. The negative CSI for the canonical housekeeping gene [GAPDH](/details-gene/2597) further challenges conventional views of cellular metabolism, suggesting a departure from standard glycolysis in this cell type. * **Testable Questions:** What is the precise protein stoichiometry of the electron transport chain complexes in these cells compared to other epithelial cells? Does selective inhibition of mitochondrial transcription versus cytoplasmic translation have differential impacts on the ion-pumping capacity of the TAL? 2. **Hypothesis:** Synaptic adhesion and signaling molecules, such as [NLGN1](/details-gene/22871) and [NRG3](/details-gene/10718), have been repurposed in the TAL to establish and maintain a highly organized tubular structure and to coordinate transepithelial transport among neighboring cells. These molecules may form "epithelial pseudo-synapses" that mediate mechanosensing or paracrine signaling in response to changes in tubular flow and solute concentration. * **Surprising Findings:** The identification of a suite of genes ([NLGN1](/details-gene/22871), [NRG3](/details-gene/10718), [PPFIA2](/details-gene/8499)) integral to neuronal synapse formation as highly specific markers for a renal epithelial cell is unexpected. This suggests that the molecular toolkit for creating complex, tightly regulated cell-cell junctions is more conserved across disparate tissues than previously appreciated. * **Testable Questions:** Using high-resolution microscopy, can [NLGN1](/details-gene/22871) and its binding partners be localized to specific cell-cell junctions in the TAL? Does targeted deletion of [Nlgn1](/details-gene/22871) or [Nrg3](/details-gene/10718) in mouse models lead to defects in TAL morphology, barrier function, or compensatory responses to diuretic stress?