Hair  - Development and Stem Cells

Structure and Function of the Hair:

Hair is a mini-organ located in the skin and serves multiple functions, including signaling and sensory roles. In mammals, thermoregulation and camouflage are provided by and are the main functions of hairy fur.

Hair is comprised of a hair follicle and hair shaft. The hair follicle is the unexposed segment of the hair that resides within the dermal layer of skin. The hair shaft originates from the hair follicle and is located both beneath and above the skin surface. The hair follicle is enclosed in the outer root sheath layer (ORS) continuous to the epidermis, and includes additional structures, such as the bulge, that serves a reservoir for hair follicle stem cells, and the sebaceous gland, that continuously produces sebum for hair lubrication. The hair shaft is comprised of three main compartments: the hair shaft (HS), the inner root sheath (IRS) that forms the channel for the protruding hair, and the companion layer that separates the IRS from the ORS.    

Embryonic and Postnatal Development of the Hair:

During embryonic mouse development, four types of hair are formed in three subsequent waves of hair induction. Guard hair represents 1-3% of total hair and is formed as a result of the first wave of hair induction initiated at E14. Awl hair comprises 30% of total hair, and is formed during the second wave starting at E16-17. Zig-zag hair makes up 65-70% of mouse hair and is formed during the third hair induction wave starting at E18.5 and continuing post-natally. Aucherine hair comprises only 0.1% of the mouse hairs and is formed during second and third hair induction waves.

Mammalian hair development is initiated in early embryogenesis and is dependent on epithelial-mesenchymal interactions. All the components of the hair are of ectodermal origin and are derived from basal keratinocytes, with the exception of the dermal papilla, which is of dermal origin and serves as a signaling center enabling proper hair initiation and growth. Hair formation includes induction, organogenesis and cytodifferentiaiton steps resulting mature hair formation.

Hair induction occurs upon 'first dermal signal' originating from dermal fibroblasts leading to the formation of epidermal placodes at approximately E13.5. Epidermal placodes are local thickenings, which define the location of the hair follicle. The underlying dermal cells then aggregate, resulting in downward placode growth, progressing toward organogenesis. The hair germ is formed by E15.5, and the peg is distinguishable by E17.5. Cytodifferentiation occurs at approximately E18.5 and is manifested by formation of the bulbous peg. At the bulbous peg stage, epithelial cells envelope the underlying dermal mesenchymal condensate, which forms the dermal papilla.

The matrix is the leading front of the proliferating peg epithelial cells, and maintains contact with the dermal papilla which supports its continuous proliferation. In mice, matrix cells proliferate for up to 18 hours and then exhaust. While proliferating, the daughter cells are pushed upwards and lose their contact with the dermal papilla. This enables them to enter a differentiation program and to give rise to the seven different types of terminally differentiated cells of the hair. HS is derived from the matrix and is comprised of three cell types: medulla, cortex and cuticle. The number of innermost medulla cell columns defines the hair thickness. Zig-zag hair has a single column of medulla cells, guard hair has two and awl hair has 2-3 columns of medulla cells. The cortex is the middle layer of the hair shaft and is the primary source of its mechanical strength. The hair shaft cuticle comprises the outer covering of the hair shaft.

The IRS is the matrix-derived cornified layer enveloping the HS, and forms a channel for the growing hair. The IRS is comprised of three distinct cell layers: the IRS cuticle, the Huxley's layer and the Henle's layer. Henle is the most outermost layer of the IRS, while the Huxley layer is located between the Henle cells and the IRS cuticle. The IRS cuticle attaches to the HS cuticle beneath the skin, but separates at the skin surface to enable hair shaft elongation. The companion layer originates from the matrix and separates the IRS from the ORS.

The ORS is divided into lower cycling and upper non-cycling regions. The non-cycling segment includes the bulge that serves as a reservoir of hair follicle stem cells. During the telogen stage, the dermal papilla and the regressed hair follicle are located adjacent to the hair bulge and signal to the stem cells to enter a differentiation program to form a new hair germ. The sebaceous gland (SG) is also situated within the non-cycling segment of the ORS. It is comprised of sebocytes that produce and secrete a lipid-rich fluid called sebum to the skin surface, responsible for protection of the skin and hair from dehydration.

During the hair life cycle, the lower part of the hair follicle continuously cycles between anagen (regeneration and growing), catagen (regression) and telogen (resting) phases. In mice, the first catagen phase follows embryonic hair morphogenesis and begins at P14, lasting for 3-4 days. The first telogen phase in mice is short and lasts for one or two days. During the subsequent postnatal hair cycle in mice, the anagen phase lasts for about 18 hours and determines the length of the hair, catagen lasts for 3-4 days and telogen for two weeks. In humans, the anagen phase can last from two to six years, and catagen for two weeks, while the length of the telogen can vary from one to four month.

Diseases of the Hair:

Hair disorders include a large variety of conditions, which can be generally categorized as detailed below.

Alopecia is the most common condition manifested by hair loss or thinning, and includes the irreversible scarring type, in which hair follicles are destroyed, and reversible non-scarring type. Androgenic alopecia, known as male pattern baldness, is an additional type of alopecia and is the most prominent type of hair disorder affecting half of the male population over 50 years of age.

Hirsutism is another hair-related disorder manifested by excessive male pattern hair growth, affecting 8% of adult women.

Hair shaft disorders are usually caused by excessive coloring or heating.