Details for: CL0000632

Cell ID: CL0000632

Cell Name: hepatic stellate cell

Description: Hepatic stellate cells are CD271-positive, desmin-positive, DDR-2-positive, GFAP-positive, synamin-positive, synaptophysin-positive, vimentin-positive, They are capable of producing angiotensin II, fibronectin, laminin, MMP-1, MMP-2, MMP-3, MMP-9, MMP-11, TGF-beta1, TIMP-1, TIMP-2, type I collagen, type III collagen, type IV collagen, and type VI collagen.

Synonyms: Ito cell, fat-storing cell, hepatic perisinusoidal cell, lipocyte, perisinusoidal cell, vitamin A-storing cells

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 hepatic stellate cell
Courtesy of SwissBioPics

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for hepatic stellate 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 hepatic stellate 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 hepatic stellate 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 hepatic stellate 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:  hepatic stellate cell (CL0000632)

 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 [hepatic stellate cell](/details-cell/CL0000632), also known as an Ito cell or vitamin A-storing cell, is a mesenchymal cell type residing in the perisinusoidal space of the liver. The **Overall** gene significance profile reveals a multifaceted identity characterized by a unique combination of high-specificity markers related to immune presentation, structural integrity, and neural-like signaling. The prominent specificity of [B2M](/details-gene/567), a core component of MHC class I, suggests a key role in hepatic immune surveillance. This is complemented by strong markers for cytoskeletal organization ([MAP1B](/details-gene/4131)) and cell adhesion ([CDH19](/details-gene/28513)), underscoring their function in maintaining the structural architecture of the liver sinusoids. ## Key Characteristics and Function Analysis of top marker genes, ranked by expression specificity (`csi_z`), elucidates several functional axes for [hepatic stellate cells](/details-cell/CL0000632). * **Immune and Inflammatory Modulation:** The most specific marker, [B2M](/details-gene/567), strongly indicates a capacity for antigen presentation via MHC class I molecules. This is further supported by the significant expression of [MIF](/details-gene/4282), a pro-inflammatory cytokine, and [C9](/details-gene/735), a component of the complement system's terminal pathway. This suggests these cells are not merely passive bystanders but active participants in the liver's immune landscape, potentially sensing and presenting antigens derived from circulation. * **Structural and Cytoskeletal Roles:** A cluster of highly specific genes points to a fundamental role in maintaining tissue structure. These include [MAP1B](/details-gene/4131) (microtubule-associated protein), [KRT8](/details-gene/3856) (keratin 8), and the cell adhesion molecule [CDH19](/details-gene/28513). This molecular signature is consistent with their anatomical position, where they interact with sinusoidal endothelial cells and hepatocytes to provide structural support. * **Metabolic Activity:** [Hepatic stellate cells](/details-cell/CL0000632) exhibit a distinct metabolic profile. The high specificity of [FTL](/details-gene/2512) (ferritin light chain) highlights their involvement in iron homeostasis, a critical function in the liver. Additionally, specific expression of [GC](/details-gene/2638) (vitamin D binding protein), [CPS1](/details-gene/1373) (a key urea cycle enzyme), and [HGD](/details-gene/3081) (involved in tyrosine metabolism) suggests a broader, specialized role in hepatic metabolism beyond their canonical function in vitamin A storage. * **Neural-like Features:** A striking and unexpected characteristic is the specific expression of numerous genes typically associated with the nervous system. These include [NRG3](/details-gene/10718) (neuregulin 3), [NRXN3](/details-gene/9369) (neurexin 3), [SYT1](/details-gene/6857) (synaptotagmin 1), and voltage-gated potassium channels ([KCND2](/details-gene/3751), [KCNIP4](/details-gene/80333)). This unique signature suggests these cells may possess sensory or signaling capabilities that integrate neural inputs with hepatic function. **Conversely**, the anti-marker profile reveals what these cells are not defined by. The low specificity for multiple components of the mitochondrial respiratory chain (e.g., [COX2](/details-gene/4513), [COX3](/details-gene/4514), [UQCRB](/details-gene/7381)) and core histone proteins ([H3 3B](/details-gene/3021)) suggests that while essential, these housekeeping functions are not uniquely prominent in stellate cells compared to other cell types. The negative CSI for immune regulators like [HMGB1](/details-gene/3146) may indicate a specialized rather than a broad-spectrum immune role. ## Clinical Significance and Contextual Roles **Overall**, the gene profile of [hepatic stellate cells](/details-cell/CL0000632) provides a molecular basis for their central role in both liver homeostasis and pathology. Their activation is a key event in the development of liver fibrosis, where they transdifferentiate into myofibroblast-like cells. The high specificity of structural genes like [MAP1B](/details-gene/4131) and [CDH19](/details-gene/28513) likely reflects their quiescent, non-fibrotic state. Dysregulation of these genes could be an early event in the activation process leading to fibrosis. The cell's involvement in iron metabolism, indicated by [FTL](/details-gene/2512), connects them to pathologies of iron overload (hemochromatosis), which can drive liver injury and fibrosis. Furthermore, their immune-modulatory potential, highlighted by [B2M](/details-gene/567) and [MIF](/details-gene/4282), positions them as key players in inflammatory liver diseases such as viral hepatitis and alcoholic steatohepatitis, where they can both respond to and perpetuate inflammatory signals. The expression of coagulation factor [F12](/details-gene/2161) also links these cells to the intricate relationship between coagulation and liver disease. The clinical relevance of the neural-like gene signature remains an emerging area, but it may implicate stellate cells in the pathophysiology of hepatic encephalopathy or nerve-mediated progression of liver disease. ## Potential Mechanisms and Research Directions 1. * **Hypothesis:** The highly specific expression of a diverse array of neural-associated genes, including neuregulins ([NRG3](/details-gene/10718)), neurexins ([NRXN3](/details-gene/9369)), and ion channels ([KCND2](/details-gene/3751)), suggests that [hepatic stellate cells](/details-cell/CL0000632) act as local signaling hubs that integrate inputs from the autonomic nervous system to regulate sinusoidal microcirculation and metabolic function. * **Surprising Findings:** The presence and high specificity of such a broad suite of synaptically-related proteins in a non-neuronal mesenchymal cell is remarkable. It challenges the traditional view of these cells as primarily involved in storage and matrix remodeling, suggesting a more sophisticated sensory and regulatory function within the liver microenvironment. * **Testable Questions:** Does selective ablation of [NRG3](/details-gene/10718) in [hepatic stellate cells](/details-cell/CL0000632) in an in vivo model alter hepatocyte zonation or the liver's metabolic response to circadian cues? 2. * **Hypothesis:** The combination of being the top specificity marker for [B2M](/details-gene/567) while showing low specificity for other immune modulators like [HMGB1](/details-gene/3146) indicates that quiescent [hepatic stellate cells](/details-cell/CL0000632) function as specialized, non-professional antigen-presenting cells. They may be uniquely positioned to sample antigens from the sinusoidal blood and present them to maintain local immune tolerance, a role that becomes pathologically pro-inflammatory upon liver injury. * **Surprising Findings:** It is unexpected that [B2M](/details-gene/567), a ubiquitous component of MHC class I, would serve as such a highly defining marker for this specific cell type. This suggests that the regulation of antigen presentation machinery is a uniquely critical aspect of the stellate cell's identity and function, potentially distinguishing it from other resident liver cells. * **Testable Questions:** Using co-culture systems, can quiescent [hepatic stellate cells](/details-cell/CL0000632) loaded with a specific peptide antigen induce anergy rather than activation in cognate [CD8-positive, alpha-beta T cells](/details-cell/CL0000625), and does this outcome switch to T-cell activation if the stellate cells are pre-treated with fibrotic stimuli like TGF-beta?