Details for: CL1000695

Cell ID: CL1000695

Cell Name: kidney interstitial alternatively activated macrophage

Description: No description available

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 kidney interstitial alternatively activated macrophage 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 interstitial alternatively activated macrophage. 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 interstitial alternatively activated macrophage. 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 interstitial alternatively activated macrophage. 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 interstitial alternatively activated macrophage (CL1000695)

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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 [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695) is a specialized macrophage subtype residing within the kidney's interstitial space. Based on its gene significance profile, this cell is characterized by an exceptionally high and specific expression of mitochondrially-encoded genes involved in oxidative phosphorylation, such as [COX1](/details-gene/4512) and [ND4](/details-gene/4538). This suggests a state of heightened metabolic activity. Concurrently, it expresses a unique suite of immune modulatory molecules like [IGSF6](/details-gene/10261) and ion transporters such as [SLC12A1](/details-gene/6557), pointing towards a sophisticated role in integrating metabolic, immune, and physiological signals within the renal microenvironment. ## Key Characteristics and Function **Overall**, the gene expression signature of the [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695) points to several core functional axes: * **Mitochondrial Bioenergetics:** A defining feature of this cell is the highly specific expression of numerous genes encoding subunits of the mitochondrial electron transport chain. This includes multiple NADH dehydrogenase subunits ([ND1](/details-gene/4535), [ND2](/details-gene/4536), [ND4](/details-gene/4538), [ND5](/details-gene/4540)) and cytochrome c oxidase subunits ([COX1](/details-gene/4512), [COX2](/details-gene/4513)), as well as [CYTB](/details-gene/4519) and [ATP6](/details-gene/4508). The high specificity (csi_z) of these mitochondrially-encoded genes suggests that this intense oxidative phosphorylation capacity is a key identifier of this cell type relative to others in the kidney, consistent with the high energy demands of M2-like macrophages involved in tissue homeostasis and repair. * **Immune Surveillance and Interaction:** The cell expresses genes indicative of active immune function. [B2M](/details-gene/567), a component of MHC class I molecules, suggests a capacity for antigen presentation to [CD8-positive, alpha-beta T cells](/details-cell/CL0000625). The high specificity of [IGSF6](/details-gene/10261), a member of the immunoglobulin superfamily, points to a role in cell-cell recognition and signaling. Furthermore, expression of [MARCHF1](/details-gene/55016), a ubiquitin ligase that regulates MHC class II levels, implies modulation of antigen presentation pathways. * **Ion Transport and Environmental Sensing:** A striking characteristic is the specific expression of a diverse set of ion channels and transporters, including the potassium channels [KCNIP4](/details-gene/80333) and [KCNMA1](/details-gene/3778), the calcium channel subunit [CACNA2D3](/details-gene/55799), and the Na-K-Cl cotransporter [SLC12A1](/details-gene/6557). The presence of [SLC12A1](/details-gene/6557) is particularly noteworthy as it is a key transporter in renal epithelial cells. This suggests a specialized function in sensing or responding to the unique and fluctuating ionic milieu of the kidney interstitium. * **Transcriptional and Post-transcriptional Regulation:** The top marker, [NEAT1](/details-gene/283131), is a long non-coding RNA that serves as a core structural component of paraspeckles, nuclear bodies involved in gene regulation. Its prominence suggests that complex post-transcriptional control mechanisms are central to maintaining the identity and function of this cell. The anti-marker profile is equally informative. The strong negative significance for ubiquitous housekeeping genes involved in transcription ([BTF3](/details-gene/689)), RNA processing ([HNRNPA1](/details-gene/3178), [DDX5](/details-gene/1655)), and protein stability ([UBC](/details-gene/7316)) suggests this cell is not in a highly proliferative state. Instead, it appears to be a more terminally differentiated cell with a specialized, rather than generalized, functional profile. The negative CSI for certain nuclear-encoded mitochondrial proteins like [COX6C](/details-gene/1345) and [COX7A2](/details-gene/1347), in stark contrast to the high CSI for mitochondrially-encoded components, may indicate the assembly of respiratory complexes with a unique subunit stoichiometry. ## Clinical Significance and Contextual Roles While this analysis is based on an **Overall** context, the specific gene markers have significant clinical implications. The high expression of genes related to alternative activation (e.g., high oxidative phosphorylation capacity) implicates these cells in processes of tissue repair and fibrosis. In the context of acute kidney injury, they may be beneficial, but in chronic disease, their sustained activity could contribute to the development of renal fibrosis. The expression of [SLC12A1](/details-gene/6557) is highly significant. Mutations in this gene cause Bartter's syndrome, a salt-wasting renal tubulopathy. Its unexpected expression in an interstitial macrophage suggests this cell could play a role in the pathophysiology of such disorders, perhaps by sensing local electrolyte disturbances or by modulating epithelial cell function. Similarly, [IGSF6](/details-gene/10261) maps to a known inflammatory bowel disease susceptibility locus ([Link](https://doi.org/10.1007/s002510000259)), hinting at a broader role for this molecule in regulating immune responses at barrier surfaces, a function that could be extrapolated to the kidney's filtration barrier. The presence of [EPCAM](/details-gene/4072), a canonical epithelial marker, is highly unusual for a macrophage and may suggest interactions with, or phagocytosis of, renal tubular epithelial cells during injury or homeostasis. ## Potential Mechanisms and Research Directions 1. **Hypothesis: Kidney interstitial macrophages act as physiological sensors that couple renal ion transport to immune regulation.** * The data suggest that [kidney interstitial alternatively activated macrophages](/details-cell/CL1000695) are uniquely equipped to monitor the local microenvironment. We hypothesize that these cells use transporters like [SLC12A1](/details-gene/6557) and various ion channels ([KCNMA1](/details-gene/3778)) not for bulk transport, but to sense changes in interstitial ion concentrations that reflect the functional state of adjacent nephron segments. This sensory information is then integrated to modulate their immune phenotype, allowing them to initiate pro-reparative or pro-inflammatory responses tailored to the specific physiological stress. * **Surprising Findings:** The expression of a gene as functionally and positionally specific as [SLC12A1](/details-gene/6557) (NKCC2) in a myeloid cell is a major unexpected observation. This challenges the conventional view of this molecule as being exclusively expressed in the thick ascending limb of the loop of Henle. The co-expression of neuronal-associated genes like [NLGN1](/details-gene/22871) further points to an unconventional sensory role. * **Testable Question:** Does pharmacologic inhibition of NKCC2 (e.g., with furosemide) directly alter the cytokine expression profile and phagocytic capacity of [kidney interstitial alternatively activated macrophages](/details-cell/CL1000695) in vitro or in vivo? 2. **Hypothesis: The unique metabolic profile of kidney interstitial macrophages is driven by a specialized stoichiometry of the electron transport chain.** * The striking dichotomy between the high specificity of mitochondrially-encoded respiratory subunits ([COX1](/details-gene/4512), [ND2](/details-gene/4536)) and the low specificity of certain nuclear-encoded subunits ([COX6C](/details-gene/1345), [COX7C](/details-gene/1350)) suggests a non-canonical assembly of respiratory supercomplexes. We hypothesize that these macrophages build a distinct form of the electron transport chain that is optimized for sustained, high-efficiency energy production required for their role in tissue surveillance and repair, which is a core feature of their "alternatively activated" state. * **Surprising Findings:** It is highly unusual for a cell's identity to be so strongly marked by an imbalance between the expression specificity of mitochondrial- versus nuclear-encoded components of the same protein complexes. This suggests a potential post-transcriptional regulatory mechanism that dictates a unique mitochondrial proteome. * **Testable Question:** Using blue native PAGE followed by mass spectrometry, do [kidney interstitial alternatively activated macrophages](/details-cell/CL1000695) exhibit a different respiratory supercomplex profile (e.g., altered ratios of Complex I, III, and IV) compared to pro-inflammatory bone marrow-derived macrophages or other resident tissue macrophages?