Hair Follicle Structure. It may serve several functions, including seasonal thermal adaptation, cleansing the body surface, elimination of defective hair follicles, and protection from malignancy (Cotsarelis, 1997; Courtois et al., 1996; Paus, 1998; Randall and Ebling, 1991). Figure 3.4. The structure of the hair shaft that is present above the epidermis. Anagen phase, 2–8 years (occasionally much longer), This page was last edited on 19 January 2021, at 01:41. Furthermore, using immunofluorescence microscopy, they demonstrated that these skin-specific Tregs predominantly reside within 0–5 μm of the bulge region, a well-established niche for HFSCs and stimulate the proliferation and differentiation of bulge HFSCs through heightened expression of Notch ligand Jag1. Early data on hair follicle growth and stem cell function suggested that the bulb of the hair follicle, containing matrix cells, is the residence of stem cells (see Costarelis et al., 1990 and references therein). Melanocytes are mixed amongst the matrix cells to provide the hair shaft with color. Hair follicle receptors sense the position of the hair. The outer root sheath cells are continuous with the basal epidermal cells and do not come into direct contact with the dermal papillae. When a club hair is completely formed, about a 2-week process, the hair follicle enters the telogen phase. It is postulated that these SC progeny then accumulate at the base of the follicle, adjacent to the DP, where they are modified to form a “lateral disc” in the bulb (Figure 64.2B). DLX3 is a crucial regulator of hair follicle differentiation and cycling.[14][15]. LRC = quiescent label-retaining cells of the bulge. The structure inside the follicle. vigorous portions of melanins of different colors combine to produce hair color. The hair is surrounded by inner and outer root sheaths. The lower, cycling part represents the actual hair shaft factory, the anagen bulb (Figure 1A). The differentiated hair follicle will eventually contain 20 or more different cell types. Denise Gay, ... George Cotsarelis, in Principles of Tissue Engineering (Fifth Edition), 2020. [1] This complex interaction induces the hair follicle to produce different types of hair as seen on different parts of the body. The internal root sheath, in turn, has three lay… The lengths of these phases are different for hairs on different parts of the body. Although this contact does not appear to be the sole source of stimulation, it seems to be a necessary stimulus to activate one or more bulge cells to divide, resulting in TA cells with decreasing levels of stemness (Costarelis et al., 1990; Taylor et al., 2000). Hair follicle has a continuous growth and rest sequence named hair cycle. Right, explanatory diagram of structure. The higher the density of the hair, the more sebaceous glands that are found. This model is based on the observation that clonogenic and morphogenic cells in the rat vibrissae are found in the bulge at any hair follicle stage, but they are found at the base of the bulb in late catagen and early anagen. The human hair follicle (HF) is a complex structure that arises developmentally through reciprocal signaling between the dermis and the overlying epidermis. Copyright © 2021 Elsevier B.V. or its licensors or contributors. A Must-Read: Toenail Clippers for Arthritic Hands. Both the HF bulb and bulge are considered to be immune-privileged sites, and collapse of these areas have been associated with inflammatory disorders resulting in hair loss [94,95], how and why the HF interacts with immune cells is still largely uncharted territory. The hair follicle begins at the surface of the epidermis. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, Comprehensive Biotechnology (Second Edition), 2011, Regenerative Biology and Medicine (Second Edition). The hair bulb forms the base of the hair follicle. [2], Hair follicles form the basis of the two primary methods of hair transplantation in hair restoration, Follicular Unit Transplantation (FUT) and follicular unit extraction (FUE). Hair follicles are epidermal invaginations that project into the dermis (Fig. Each strand of hair consists of three layers. For a helpful visual, think of the hair follicle as a vase and the hair as the stem of a flower. When a hair is forcibly plucked, or the follicle damaged by chemotherapy, catagen occurs prematurely and telogen is drastically shortened to bring the follicle to anagen quickly. The differences in appearance and texture of hair are due to many factors: the position of the hair bulb relative to the hair follicle, size and shape of the dermal papilla, and the curvature of the hair follicle. 2. This hypothesis was hard to explain because of the cycling nature of the bulb, which undergoes extensive apoptosis in catagen, leaving only a small strand of epithelial cells connecting the DP and the bulge. We have synthesized hair follicle-specific keratins from the companion layer (K6hf, K17) and the hair cortex (Ha1, Hb3, Hb6) in Escherichia coli. Structure Inside Follicle A. It exists within the dermis and the epidermis, the two top layers of the skin. Hair Bulb. They also found that the production of CCL2 and CCL20 chemokines by HF keratinocytes is responsible for the recruitment of LCs and pre-LCs to the epidermis, further illustrating HF keratinocytes as a potent source of proteins regulating immune cell trafficking into the skin. Scalp hair stays in this active phase of growth for 2–7 years; this period is genetically determined. When matrix TA cells cease dividing, perhaps through exhaustion of their proliferative capacity, the bulb of the hair follicle undergoes apoptosis (catagen phase). The 3 layers of hair… Recently, an additional epithelial stem cell niche has been identified in the bulge region of the hair follicle, near the insertion site of the arrector pili muscle.15 There has been active interest in these populations, with respect to their contributions to re-epithelialization, as well as to their potential to differentiate along adnexal lines. Within the stratum corneum, there is a gradient of the pH from approximately 7 at the stratum granulosum to 5 at the skin surface. Copyright 2011, Elsevier. 3.4). A hair follicle forms a bulb around the specialized dermal cells, the dermal papillae. The hair follicle regulates hair growth via a complex interaction between hormones, neuropeptides, and immune cells. [1] The process of hair growth occurs in distinct sequential stages. Well known diseases of the hair follicle include alopecia or hair loss, hirsutism or excess hair growth, and lupus erythematosus. The epithelial root sheath is an extension of the epidermis; it consists of stratified squamous epithelium and lies immediately adjacent to the hair root. [24], A photograph of hair on a human arm emerging from follicles, "Histologic Diagnosis of Inflammatory Skin Diseases, Chapter 1. It not only forms an extremely resistant and strong barrier against external insults but also limits the diffusion of water molecules from the highly hydrated keratinocytes to the outside [11]. Only 1–2% of hairs are in catagen at a given time, and individual follicles spend 2–3 weeks in this phase. Stem cells in the lower and middle bulge regenerate the hair, while stem cells in the upper bulge and isthmus renew the non-hair parts of the follicle (Brownell et al., 2011). It is the lowest part of your hair strand, which lies inside the follicle. It is this miniaturization of the hair shaft that is the primary predictive indicator of androgenetic alopecia,[20] commonly referred to as male pattern baldness or male hair loss. [1] The scalp hair follicle in Caucasians is elliptical in shape and, therefore, produces straight or wavy hair, whereas the scalp hair follicle of people of African descent is more curvy, resulting in the growth of tightly curled hair. Up to 90% of the hairs on the human scalp are in anagen at any one time, and this phase can occupy anywhere from 2–7 years for a given hair. Neural crest cells normally differentiate into the pigmented cells of the hair, but in clonal culture they form colonies containing neurons and smooth muscle cells, as well as melanocytes, and can be induced by neuregulin-1 (glial growth factor-1) and BMP-2 to differentiate into Schwann cells and chondrocytes, respectively (Sieber-Blum et al., 2004). The hair that you see is called the hair shaft. During catagen and early anagen, these bulge cell derivatives accumulated at the base of the hair follicle in a relatively undifferentiated state. A club hair is formed during the catagen phase when the part of the hair follicle in contact with the lower portion of the hair becomes attached to the hair shaft. Copyright 2010, American Association for the Advancement of Science. [1] It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. This phase lasts for about 2–3 weeks while the hair converts to a club hair. Figure 3.3. From drug delivery point of view, sebum may serve as a vehicle for drugs that are soluble in it. Known as “hair follicle predetermination,” this model is based on multiple studies of hair follicle growth (Panteleyev et al., 2001), and although speculative, it offers an alternative explanation for conflicting results (Silver et al., 1969; Morris and Potten, 1999). Aging of the hair follicle appears to be primed by a sustained cellular response to the DNA damage that accumulates in renewing stem cells during aging. Each of the three types of follicle on … The walls of the hair follicle above the matrix form the inner and outer root sheaths. Normally up to 90% of the hair follicles are in anagen phase, while 10–14% are in telogen and 1–2% in catagen. For a number of years, epidermal stem cells were believed to reside exclusively at the tip of rete ridges within the basal cell layer. Recently, Wang et al. It consists of the Hair matrix cells, as well as melanocytes, (pigment forming cells), which surround the Dermal Papilla. 3.3). The predominant cells in the sebaceous gland, sebocytes, secrete lipid-rich products into the infundibular opening of the adjacent hair follicle. This suggests that bulge cells and epidermal stem cells are intrinsically different, in that epidermal-derived cells seem better suited for establishing long-term epidermal proliferative units. The follicle is the essential unit for the generation u0003of the hair shaft. [1] Differences in the shape of the scalp hair follicle determine the observed ethnic differences in scalp hair appearance, length and texture. The epidermis is interrupted by hair follicles and sweat glands, except at the palms and soles where no hair follicles are present. More than 60% of men and 10% of women suffer from hair loss. 6.3) are comprised of pockets of epithelium, which are continuous with the superficial epidermis and extend deep into the dermis. This “acid mantle” facilitates the growth of the residual skin flora, hereby inhibiting pathologic microbial colonization. It houses several types of stem cells, which supply the entire hair follicle with new cells, and take part in healing the epidermis after a wound. Your hair is made of two parts - the hair follicle and the hair shaft. 1. Top panels, reproduced with permission from Barker et al., Tissue resident adult stem cell populations of rapidly self-renewing organs, Cell Stem Cell 7:656–670. Hair formation, hair follicle or pilli development, is an excellent example of two distinct developmental processes: epithelio-mesenchymal interactions and pattern formation. Interestingly, they found that LCs were almost completely absent from the epidermis of scalps from subjects with lichen planopilaris, a condition characterized by inflammation and destruction of the HF bulge, corroborating the portal role of follicles and also hinting at the potential of immunomodulation as a treatment of lichen planopilaris. red hair color is pigmented by trichosidern, gray and white is from decreased melanin production and … Such contact occurs at the end of each hair cycle, as the surrounding dermal sheath shrinks during the apoptotic phase, and drags the DP upward until it comes into contact with the bulge. The hair follicle consists of a complex system of multiple tissue compartments that are clearly distinguishable by their morphology and type of differentiation. Proteolysis of collagen leads to elimination of the damaged cells and then to terminal hair follicle miniaturization. DP = dermal papilla, CT = connective tissue sheath surrounding the follicle, ERS = external root sheath (outer root sheath), GM = the glassy membrane that separates the external root sheath from the outer connective tissue layer, IRS = internal root sheath, Cx = the highly keratinized cortex of the hair shaft, M = the medulla or core of the hair shaft, Cu = the thin cuticle that covers the surface of the hair shaft. Evidence that the bulge contains a large pool of LRCs, together with the appealing location of the bulge as a “niche” at the base of the permanent portion of the hair follicle, suggested a novel model for hair follicle growth, the “bulge activation hypothesis” (Figure 64.2C) (Costarelis et al., 1990). [17] It signals the end of the active growth of a hair. Stem cells in the bulge region of the HF and the dermal papilla cells are the main regulators of the hair cycles. The hair shaft consists of a cortex and cuticle cells, and a medulla for some types of hairs. This curved region is called the infundibulum. The outer root sheath and the matrix contain neural crest-derived cells. Bulge stem cells are then activated to self-renew and replenish the hair germ stem cells. Hair is a derivative of the epidermis and consistsu0003of two distinct parts: the follicle and the hair shaft. The main structure of hair consists of the root, hair follicle, and the hair shaft. In addition to its role in defining human appearance, scalp hair also provides protection from UV sun rays and is an insulator against extremes of hot and cold temperatures. depleted LCs in Langerin-DTR (diphtheria toxin receptor) mice by injection of diphtheria and then undertook bone marrow reconstitution with CAG-eGFP bone marrow to follow eGFP-labeled LC differentiation and skin reconstitution in vivo. Bulb. [10], There are many human diseases in which abnormalities in hair appearance, texture or growth are early signs of local disease of the hair follicle or systemic illness. Copyright 2010, Elsevier. The stratum corneum forms the outermost part of the skin and is in direct contact to the environment. When Ly6C+ macrophages were depleted in the wound region, both WIH-A and WIHN were attenuated. For example, terminal hairs grow on the scalp and lanugo hairs are seen covering the bodies of fetuses in the uterus and in some newborn babies. Hair grows in cycles of various phases:[13] anagen is the growth phase; catagen is the involuting or regressing phase; and telogen, the resting or quiescent phase (names derived using the Greek prefixes ana-, kata-, and telos- meaning up, down, and end respectively). The hair shaft consists of an inner core known as the medulla. Hair follicle (replete with its stem cell niche) is not a trivial structure in Homo sapiens. At most hairy skin areas, the epidermis is approximately 70 μm thick [8,9] and it is much thicker at the heels and palms. The key rate-limiting role of Blimp1 in sebaceous gland homeostasis was revealed following epithelial Blimp1 deletion, which led to sebaceous gland hypertrophy and oily hair coat phenotype [33]. There are ethnic differences in several different hair characteristics. The hair follicle is a diagonal tube that contains the hair root. With respect to hair shape, it is now established that hair curliness is programmed from the bulb and is linked to asymmetry in the different hair follicle compartments. Furthermore, Castellana et al. At least 25% of the newly formed epidermis originated from the bulge cells. As a result, your hair grows longer. The catagen phase is a short transition stage that occurs at the end of the anagen phase. While the unquestionable importance of macrophages in wound healing has been known for many years, we are only beginning to elucidate their roles in HF and HFSC regeneration. Hair Structure and Life Cycle Hair is composed of strong structural protein called keratin. To better understand trafficking of these dendritic cells into the skin, Nagao et al. At the end of catagen, a small cluster of cells derived from the bulge, the hair germ, forms between it and the dermal papilla (Greco et al., 2009). (2001) discovered that stem cells or their more or less committed progeny appeared to migrate along the ORS to come in contact with the DP, which then seemed to signal their pathway to differentiate. Then hair cells undergo apoptosis during catagen to retract the dermal papilla toward the hair germ to achieve the telogen resting phase, whereupon the cycle begins again. But the origin of LCs in HFs is still incompletely understood. The proximal tip of the follicle is invaginated to form a cap over the dermal papilla, a condensation of dermal fibroblasts associated with the follicle (Hardy, 1992). The hair shaft is formed by the proliferation and differentiation of the matrix cells upward through the lumen of the follicle. In addition, it contains a small amount of lipids and water. When cells exit the bulge and migrate upward, they take on the fate of a TA epidermal or SG cell. ), Skin appendages include the pilosebaceous apparatus, eccrine sweat glands and apocrine glands. Based on the recent H2B-GFP LRC study, it would seem that a modification of the predetermination model is now warranted to explain how, possibly as a secondary step following the initial “lateral disk” activation, the H2B-GFP LRCs are stimulated to exit the bulge area, proliferate, and participate in the formation of the matrix, all within a single anagen (Tumbar et al., 2004). The cycle's length varies on different parts of the body. The hair follicle is surrounded by a protective root sheath, consisting of the external and internal root sheath. This is the same kind of protein that makes up the nails and the outer layer of skin. The hair shaft is formed by the proliferation and differentiation of the matrix cells upward through the lumen of the follicle. A sheath of dermal cells surrounds each hair follicle. Rabinarayan Parhi, in Applications of Nanocomposite Materials in Drug Delivery, 2018. 3.2). During these three phases, the lower portion of the follicle goes through cyclic growth and regression, while the upper region of the follicle, including the sebaceous gland, the isthmus, the infundibulum, and the hair canal, remains permanent. Because many enzymes involved in epidermal differentiation are pH dependent, pH also exerts direct effects on the stratum corneum cohesion, desquamation, and permeability homeostasis [12]. In the first step, the hair germ cells proliferate, followed in the second step by proliferation of bulge cells, pushing the dermal papilla downward to reconstitute the hair bulb and matrix. The lower most portion of a mature hair follicle (bulb) contains mitotically active germinative cells (which produce the hair shaft in a manner somewhat analogous to epidermal keratinization).14 Eccrine sweat glands main function is thermoregulation, which is accomplished through excreting sweat. Additionally, several regions have been identified in complex hair diseases such as alopecia areata and androgenetic alopecia through genome-wide association studies (GWAS). D.T. Well known diseases of the hair follicle include alopecia or hair loss, hirsutism or excess hair growth and lupus erythematosus. [12] This damage response involves the proteolysis of type XVII collagen by neutrophil elastase in response to the DNA damage in the hair follicle stem cells. Bulge cells were also stimulated to move into the epidermis following incisional wounds and after tape stripping, indicating that bulge cell activation plays a role in replenishing lost cells from the epidermis after wounding. [100] depleted Ly6C+ monocytes and macrophages in mouse skin and noted delayed anagen in the wound-induced hair anagen reentry/growth (WIH-A) model, as well as in WIHN. made by melanocytes at the base of the hair follicle and transferred to the cortical cells. 6.3) are comprised of pockets of epithelium, which are continuous with the superficial epidermis and extend deep into the dermis. A key aspect of hair loss with age is the aging of the hair follicle. A seemingly difficult task of classifying and stratifying various follicular tumours can be made easier by grouping various follicular tumours according to lines of differentiation pertaining to the specific anatomical compartments within the hair follicle. Other structures associated with the hair follicle include the cup in which the follicle grows known as the infundibulum,[7] the arrector pili muscles, the sebaceous glands, and the apocrine sweat glands. Stages in the adult hair regeneration cycle, clockwise from early anagen. Bottom: A more detailed map of stem cell marker expression domains that includes the Gli-1 expressing domains of the bulge. At least in neonate and wounded adult skin, stem cell activation may be accompanied by a flux of upper ORS cells to the epidermis. However, the role of the bulge cells in wound healing has only recently been characterized. Of all mammals, humans have the longest growth phase of scalp hair compared to hair growth on other parts of the body. Hair consists of mostly fibrous protein (65-95 %). Hair is made of a tough protein called keratin. However, its persistence in humans provides a unique opportunity to probe the mysteries of how complex structures regenerate in the adult. A hair follicle anchors each hair into the skin. In fact, macrophages have been implicated to be essential in homeostatic hair growth. Cotsarelis, 1997; Courtois et al., 1996; Paus, 1998; Randall and Ebling, 1991. Apart from a protective role, mammalian HFs are a reservoir for various immune cells. The telogen phase is short if not absent from vibrissae, and a new vibrissae cycle is initiated before the DP has moved upward completely to come into contact with the bulge.