Details for: CL1000452

Cell ID: CL1000452

Cell Name: parietal epithelial cell

Description: An epithelial cell that is part of the glomerular parietal epithelium.

Synonyms: epithelial cell of parietal layer of glomerular capsule

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 parietal epithelial cell
Courtesy of SwissBioPics

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for parietal 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 parietal 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 parietal 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 parietal 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:  parietal epithelial cell (CL1000452)

 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 [parietal epithelial cell](/details-cell/CL1000452) is a specialized epithelial cell forming the outer wall of the glomerulus, also known as Bowman's capsule. Based on its gene significance profile, this cell type is characterized by an exceptionally high metabolic rate, indicated by top markers involved in mitochondrial respiration such as [ND5](/details-gene/4540) and [ND2](/details-gene/4536). Furthermore, the prominence of genes associated with RNA processing, including the top marker [DDX17](/details-gene/10521), suggests that these cells maintain a complex and highly regulated transcriptional and post-transcriptional landscape. This combination of high energy production and intricate gene regulation is consistent with their role in maintaining the structural integrity of the glomerulus and potentially acting as local progenitor cells during injury and repair. ## Key Characteristics and Function The molecular signature of the [parietal epithelial cell](/details-cell/CL1000452) points to several core functional axes. * **Epithelial Identity and Barrier Function:** As expected for an epithelial cell, several markers confirm its structural role. These include the epithelium-specific transcription factor [ELF3](/details-gene/1999) ([Link](https://doi.org/10.1128/mcb.17.8.4419)), the cytokeratin [KRT8](/details-gene/3856), and components of cell junctions such as [CLDN4](/details-gene/1364) (claudin-4) and [CCDC85A](/details-gene/114800) (adherens junctions). The high significance of [KIRREL3](/details-gene/84623), a homolog of the podocyte protein nephrin ([Link](https://doi.org/10.1096/fj.02-0242fje)), further underscores its specialized role within the glomerulus and suggests potential cell-cell communication with adjacent podocytes. * **Intense RNA Processing and Regulation:** A defining feature of this cell is the high significance of genes involved in RNA metabolism. The top marker, [DDX17](/details-gene/10521), is a DEAD-box RNA helicase crucial for alternative splicing. This is complemented by other highly significant genes like the long non-coding RNA [NEAT1](/details-gene/283131), the splicing regulator [RBFOX1](/details-gene/54715), and the heterogeneous nuclear ribonucleoprotein [HNRNPC](/details-gene/3183). This robust RNA processing machinery may enable the cell to fine-tune its proteome in response to physiological cues or pathological insults. * **High Mitochondrial Energy Metabolism:** The exceptional `csi_z` scores for mitochondrial DNA-encoded genes like [ND5](/details-gene/4540), [ND2](/details-gene/4536), and [COX1](/details-gene/4512) indicate a profound reliance on aerobic respiration. This high energy demand is likely necessary to power active transport processes, maintain the glomerular filtration barrier, and support cellular plasticity. * **Complex Signaling Capacity and Neural-like Features:** **Overall**, a surprising and prominent theme is the expression of genes typically associated with the nervous system. This includes [NRG3](/details-gene/10718) (Neuregulin-3), the voltage-gated sodium channel [SCN2A](/details-gene/6326), the potassium channel interacting protein [KCNIP4](/details-gene/80333), and the synaptic organizing protein [NETO1](/details-gene/81832). This signature suggests that parietal epithelial cells may participate in complex, non-canonical signaling pathways within the renal microenvironment, potentially responding to or emitting neuro-modulatory signals. The presence of the [PTH2R](/details-gene/5746) receptor also points to a role in endocrine signaling. The anti-marker profile further refines this identity. The low relative significance of ubiquitous RNA-binding proteins like [DDX5](/details-gene/1655) and [YBX1](/details-gene/4904) suggests a specialized, rather than general, RNA regulatory network, highlighted by the specific prominence of [DDX17](/details-gene/10521). ## Clinical Significance and Contextual Roles **Overall**, the gene signature of parietal epithelial cells provides insights into their potential roles in kidney health and disease. These cells are implicated as cells of origin for the cellular crescents that characterize rapidly progressive glomerulonephritis, and their marker profile aligns with this proliferative and adaptive potential. The high expression of [ELF3](/details-gene/1999), an Ets-family transcription factor linked to epithelial tumorigenesis ([Link](https://doi.org/10.1038/sj.onc.1200978)), is consistent with the cell's capacity for pathological proliferation. Similarly, the expression of [TXNIP](/details-gene/10628), a key regulator of cellular redox state, suggests these cells are equipped to sense and respond to oxidative stress, a common feature of kidney injury. The striking enrichment for "neural" genes has potential clinical implications. [NRG3](/details-gene/10718) is a ligand for ErbB4 receptors and has been implicated in neural development and schizophrenia ([Link](https://doi.org/10.1073/pnas.94.18.9562)). Its role in the kidney is unknown but may relate to cellular growth and differentiation. Similarly, mutations in [SCN2A](/details-gene/6326) are known to cause severe neurological disorders. Its specific expression in parietal epithelial cells may point to a previously unappreciated role for ion channel signaling in glomerular function or pathology, which could be dysregulated in certain forms of kidney disease. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** Parietal epithelial cells utilize a "neural-like" signaling repertoire, including neuregulins and voltage-gated ion channels, to communicate with other glomerular cells (e.g., podocytes, mesangial cells) and regulate glomerular homeostasis and injury response. This signaling may modulate filtration dynamics or coordinate cellular repair processes. * **Surprising Findings:** The co-expression of a suite of genes traditionally considered neuron-specific, such as [NRG3](/details-gene/10718), [SCN2A](/details-gene/6326), and [NETO1](/details-gene/81832), within a renal epithelial cell is highly unexpected and suggests a functional convergence between these distinct tissues. * **Testable Questions:** Does paracrine stimulation with Neuregulin-3 (the protein product of [NRG3](/details-gene/10718)) alter gene expression or calcium signaling in co-cultured podocytes? Furthermore, does pharmacologic modulation of the SCN2A sodium channel in kidney organoids affect glomerular permeability or the parietal epithelial cell response to injury? 2. **Hypothesis:** The highly specific RNA processing machinery, dominated by the DEAD-box helicase [DDX17](/details-gene/10521), is critical for the cell's function as a facultative progenitor. This machinery may control key alternative splicing events that govern the switch between a quiescent state and a proliferative, migratory phenotype observed in crescentic glomerulonephritis. * **Surprising Findings:** The stark contrast between the high significance of [DDX17](/details-gene/10521) as a top marker and the negative significance of its close paralog, [DDX5](/details-gene/1655), strongly suggests a non-redundant, highly specific role for [DDX17](/details-gene/10521) in the unique biology of this cell. * **Testable Questions:** What are the specific mRNA targets and alternative splicing events regulated by [DDX17](/details-gene/10521) in human parietal epithelial cells? Does shRNA-mediated knockdown of [DDX17](/details-gene/10521) *in vitro* impair the proliferative or migratory response of these cells to pro-inflammatory stimuli like TGF-beta or IL-1?