Details for: CL4028004

Cell ID: CL4028004

Cell Name: alveolar type 1 fibroblast cell

Description: A pulmonary interstitial fibroblast that is part of the alveolus and contains lipid droplets.

Synonyms: alveolar fibroblast 1, alveolar fibroblast, lipid interstitial cell, lipofibroblast, matrix fibroblast 1, pulmonary lipofibroblast, AF1

Selected Context(s): Overall

Gene Significance Landscape

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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

Image representation

Depiction of alveolar type 1 fibroblast cell
Courtesy of SwissBioPics

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for alveolar type 1 fibroblast 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 alveolar type 1 fibroblast 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 alveolar type 1 fibroblast 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 alveolar type 1 fibroblast 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:  alveolar type 1 fibroblast cell (CL4028004)

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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):
 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 **Overall** gene significance profile identifies the [alveolar type 1 fibroblast cell](/details-cell/CL4028004) as a metabolically active, structural cell with significant roles in calcium-dependent signaling, immune surveillance, and iron homeostasis within the pulmonary interstitium. Its identity is strongly defined by the specific expression of the calcium-binding protein [S100A6](/details-gene/6277) (CSI: 73.45), suggesting a primary function in dynamic, signal-responsive processes rather than solely static matrix production. The high significance of [B2M](/details-gene/567) (CSI: 66.51), a core component of the MHC class I complex, points towards an unappreciated role in interacting with the adaptive immune system, particularly in antigen presentation. The cell's synonym, lipofibroblast, is consistent with a high metabolic state, supported by the prominence of multiple mitochondrial and metabolic pathway genes among its top markers. ## Key Characteristics and Function Analysis of the most specific gene markers for the [alveolar type 1 fibroblast cell](/details-cell/CL4028004) reveals several key functional clusters that define its biological role. * **Calcium Signaling and Cytoskeletal Dynamics:** The most significant marker, [S100A6](/details-gene/6277) (CSI: 73.45), is a calcium-binding protein implicated in cell growth and structure ([Link](https://doi.org/10.1016/s0021-9258(18)67137-6)). This is complemented by other calcium-binding proteins like [TPT1](/details-gene/7178) and [CALM2](/details-gene/805). This strong calcium-related signature suggests that the cell is highly responsive to intracellular calcium fluxes, which may regulate contractility, secretion, or cytoskeletal rearrangement. The high specificity of [MAP1B](/details-gene/4131) further points to an active role in organizing the microtubule cytoskeleton. * **Metabolic Activity and Iron Homeostasis:** A suite of genes involved in energy metabolism are defining markers, including mitochondrial components like [CYTB](/details-gene/4519), [ND1](/details-gene/4535), and [COX2](/details-gene/4513). This indicates a high energetic demand. Concurrently, the high significance of both light and heavy ferritin chains, [FTL](/details-gene/2512) (CSI: 65.70) and [FTH1](/details-gene/2495) (CSI: 43.68), highlights a specialized function in iron storage and management. This is critical for mitochondrial function and for protecting against iron-induced oxidative stress, a constant threat in the oxygen-rich lung environment. The expression of [GSTP1](/details-gene/2950) further supports a role in mitigating oxidative damage. * **Immune System Interaction:** The high specificity score for [B2M](/details-gene/567) (CSI: 66.51), an essential subunit of MHC class I molecules, strongly suggests these fibroblasts participate in immune surveillance by presenting endogenous antigens to cytotoxic T lymphocytes. This positions them as potential sentinels that can signal cellular stress or viral infection to the immune system. * **Transcriptional and Translational Activity:** The cell exhibits markers of robust transcriptional regulation ([JUN](/details-gene/3725)) and high translational activity ([EEF1D](/details-gene/1936), [PABPC1](/details-gene/26986)). The presence of [NEAT1](/details-gene/283131), a long non-coding RNA involved in nuclear paraspeckle formation, implies sophisticated control over gene expression and mRNA processing. * **Negative Markers:** The low significance of several common signaling adapter proteins, such as [YWHAZ](/details-gene/7534) and [YWHAB](/details-gene/7529) (14-3-3 proteins), and specific G-protein subunits like [GNAS](/details-gene/2778), may indicate that this cell utilizes specific, curated signaling pathways and is not a generalist responder. The relatively low scores for some essential housekeeping genes like [GAPDH](/details-gene/2597) and multiple mitochondrial genes like [COX3](/details-gene/4514) and [ND4](/details-gene/4538) suggest a highly specialized metabolic profile rather than a generic one. ## Clinical Significance and Contextual Roles **Overall**, the gene profile of the [alveolar type 1 fibroblast cell](/details-cell/CL4028004) suggests it plays a critical, multifaceted role in both lung homeostasis and pathology. As interstitial fibroblasts are key drivers of pulmonary fibrosis, the high significance of pro-fibrotic signaling components like the transcription factor [JUN](/details-gene/3725) is clinically relevant. This gene is an immediate-early response gene, and its prominence may indicate the cell's readiness to respond to alveolar injury, a process which, if dysregulated, can lead to fibrotic scarring. The cell's pronounced iron-handling capacity, evidenced by high [FTL](/details-gene/2512) and [FTH1](/details-gene/2495) expression, could be central to diseases characterized by iron dysregulation in the lung. For example, excess iron can catalyze the formation of reactive oxygen species, and the ability of these fibroblasts to sequester iron may be a crucial protective mechanism. In conditions like idiopathic pulmonary fibrosis, altered iron metabolism is an emerging area of research, and these cells are likely central players. Furthermore, their apparent role in antigen presentation via [B2M](/details-gene/567) expression implies they could be involved in the pathogenesis of viral lung infections or autoimmune diseases affecting the lung. By presenting viral antigens, they could flag infected areas for clearance by [CD8-positive, alpha-beta T cells](/details-cell/CL0000625). Conversely, in autoimmune contexts, they might erroneously present self-antigens, contributing to chronic inflammation. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The [alveolar type 1 fibroblast cell](/details-cell/CL4028004) functions as a key mechanosensor and regulator of alveolar structural integrity, with its activity being dynamically tuned by calcium signaling rather than primarily through static extracellular matrix deposition. * **Surprising Findings:** The most specific marker for this fibroblast is not a collagen or matrix-remodeling enzyme but [S100A6](/details-gene/6277), a calcium-binding protein. This suggests its primary role may be more dynamic and regulatory, responding to mechanical stretch and other signals via calcium-dependent pathways that modulate cytoskeletal tension. * **Testable Questions:** Does subjecting these fibroblasts to mechanical stretch in vitro induce measurable changes in intracellular calcium concentration, and does the knockdown of [S100A6](/details-gene/6277) or [MAP1B](/details-gene/4131) alter their contractile properties or their ability to organize collagen matrices in 3D culture? 2. **Hypothesis:** Beyond their structural role, [alveolar type 1 fibroblast cells](/details-cell/CL4028004) act as local immune modulators, using their prominent MHC-I machinery ([B2M](/details-gene/567)) for antigen presentation and their iron-sequestration capacity ([FTL](/details-gene/2512)/[FTH1](/details-gene/2495)) to influence the function and survival of nearby immune cells. * **Surprising Findings:** It is unexpected for a cell primarily defined as a fibroblast to exhibit such a strong gene signature for MHC class I-mediated antigen presentation. This places it in a unique position at the interface of structural support and immune surveillance. The tight linkage with a highly specific iron metabolism signature suggests these two functions may be co-regulated. * **Testable Questions:** In a co-culture system, can interferon-gamma-stimulated [alveolar type 1 fibroblast cells](/details-cell/CL4028004) that have been pulsed with a known peptide antigen effectively activate peptide-specific [CD8-positive, alpha-beta T cells](/details-cell/CL0000625)? Furthermore, does manipulating intracellular iron levels by silencing [FTH1](/details-gene/2495) alter the magnitude of this T-cell activation?