Basal cell

A basal cell is a cell type that is present in many forms of epithelial tissue throughout the body. It is generally located between the basement membrane and the rest of the epithelium.

They can interact with neurons, the basement membrane, columnar epithelium, and underlying mesenchymal cells from this pivotal position. They also engage in interactions with dendritic, lymphocyte, and inflammatory cells. The lateral intercellular gap between basal cells is where these interactions occur.

Basal cells have important health implications since the most frequent types of skin cancer are basal cell and squamous cell. More than 1 million instances of non-melanoma skin cancers (NMSC) are expected to be diagnosed in the United States each year, and the incidence is rapidly increasing. Basal and squamous cell malignancies, while seldom metastatic, can cause significant local damage and disfigurement, affecting large sections of soft tissue, cartilage, and bone.

Location

Basal cells are located in various tissues throughout the body. They are located at the bottom of epithelial tissues, generally situated between the basement membrane and the remainder of the epithelium. Examples include:

• Epidermal cells in the stratum basale
• Airway basal cells, which are respiratory cells located in the respiratory epithelium (found in decreasing concentrations as airway diameter decreases)
• Basal cells of prostate glands
• Basal cells of the Gastrointestinal tract mucosal layer

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  Layer of columnar or cuboidal basal cells in the basal layer of the skin
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  Prostate gland microanatomy, with basal cells found between the luminal cells and the basement membrane.
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  Cells of the respiratory epithelium. Basal cells shown in purple, ciliated cells shown in brown, goblet cells shown in green, and submucosal gland shown in blue.

Structure

Regardless of their specific location, basal cells generally share a similar basic structure. They are all usually either cuboidal, polyhedral or pyramidal shaped cells with enlarged nuclei and minimal cytoplasm. Basement cells are bound to each other by desmosomes, and to the basal lamina of the basement membrane by hemidesmosomes. These junctions help to create one tightly bound, continuous tissue layer that can endure mechanical stress and effectively function as a connection between the basement membrane and remaining epithelial tissue.

Function

Basal cells serve two main functions in cells. They serve:

1. To anchor and connect the epithelium to the basal membrane
2. As the main stem cell population for the tissue they are found in

While all basal cells, regardless of location, function similar in regards to anchoring the epithelium, the specific function and mechanisms of basal cells as stem cells varies by location. In general, basal cells can can function as either unipotent or multipotent stem cells.

Epidermal basal cells

In the epidermis, basal cells function as unipotent stem cells. Found in the lowest layer of the epidermis, the stratum basale, basal cells continuously divide in order to replenish the squamous cells that make up the skin's surface. Every time a basal cell divides, it creates two daughter cells, one is an identical basal cell, and the other is a new somatic cell that undergoes terminal differentiation. These cells gradually get pushed up through the layers of the epidermis by the constant proliferation of more new cells, gradually differentiating and flattening as they rise. This ultimately results in functional squamous cells on the outermost layer of the epidermis, the most abundant of which are called keratinocytes.

The continuous division of epidermal basal cells leads to complete epidermal turnover every 40-56 days in humans and every 8-10 days in mice.

This process of proliferation and differentiation is regulated by multiple genetic and environmental factors including a calcium gradient, Vitamins A and D, epidermal growth factor (EGF), transcription factor p63, and transforming growth factor alpha (TGF-α).

Errors in the regulatory mechanisms of epidermal basal cells can cause a variety of acute and chronic ailments including psoriasis and basal cell carcinoma, which is the most common type of skin cancer, accounting for 80% of all skin cancer cases. Due to the structural importance of the epidermis, defects in basal cell proliferation and differentiation can also contribute to deformities such as cleft lips and Gorlin syndrome.

Respiratory basal cells

In the respiratory tract, basal cells function as multipotent stem cells, capable of replenishing all of the epithelial cell types including secretory, ciliated, and intermediate cells. They reside in the mucosal layer of the respiratory epithelium, and generally remain dormant. However, when a functional epithelial cell becomes damaged, a basal cell is activated to differentiate into the appropriate cell type and replace the damaged cell.

In addition to functioning as stem cells, there is novel evidence to suggest that undifferentiated basal cells also contribute immune functions of the respiratory epithelium by secreting RNase. This function helps to preserve the immune capabilities of the respiratory epithelium even when it is damaged and in the process of being repaired.

In the respiratory epithelium, there exists a layer of intermediate cells between the basal and differentiated cells. These intermediate cells exist in a transient state. They have begun the process of differentiation, but are not yet terminally differentiated, and as such can differentiate as needed, but have limited proliferative capacity. They play an important role in ensuring that the epithelium can be quickly repaired in response to damage.

The process of respiratory basal cell differentiation is regulated by multiple factors including genes such as FOXJ1 and FOXA3, transcription factors such as Sox2, p53, LEF-1, and external factors such as cytokines and interleukins IL-1α and IL-33. The primary control of basal respiratory cell differentiation is the NOTCH signaling pathway, which is the main determinant of what the basal cell differentiates into. High levels of NOTCH activity leads to secretory differentiation, whereas low levels lead to differentiation into a ciliated cell.