Hair follicle differentiation and regulation the international journal. Very recently, mutations in an epithelial keratin of the hair follicle inner root sheath have been linked to autosomal dominant woolly hair, again showing that a structural abnormality of the epithelial layers surrounding the hair shaft can lead to abnormal hair structure. Five million total hair follicles in the adult human, without significant racial or sexual differences scalp has highest density, but declines with age from 15cm 2 at birth to 300500cm 2. Hair graying is a ubiquitous, visible, and early feature of human aging. Substantial progress has been made regarding the elucidation of differentiation processes of the human hair follicle. Plucked beard hairs from two volunteers were freed from adhering outer and inner root sheaths as described. The genes that are expressed before the signs of hair follicle formation constitute the precise spacing and distribution of the follicles. We report for the first time the successful maintenance and growth of human hair follicles in vitro. Characterization of hair follicle antigens targeted by the. The viscoelastic properties of chemically modified. These proteins allow tissues to resist damage from friction and minor trauma, such as rubbing and scratching. Thus, there are 28 type i keratin genes 17 epithelial keratins and 11 hair keratins and 26 type ii keratin genes 20 epithelial keratins and 6 hair keratins.
Extraction of hair keratins, one and twodimensional gel electrophoresis, and western blot procedure. Specific antisera against the individual hair keratins were used to establish the twodimensional catalog of human type ii hair keratins. The lactiferous ducts also open up into the infundibulum of. After the elucidation of the human type i hair keratin genes and their expression patterns in the hair follicle as well as the assembly of the encoded proteins into a catalog, the extension of these studies to type ii hair keratins became mandatory. Fusenig im neuenheimer feld 280, d6900 heidelberg, federal republic of germany. The stiffness of the hair follicle is expected to extend over several orders of. Recent discovery of hair follicle keratin 75 krt75 in enamel raises questions about the function of this protein in enamel and the mechanisms of its secretion. In the human genome, the keratin genes are clustered at two diverent chromosomal sites. A highyield twohour protocol for extraction of human. Embryonic stages of the human hair follicle morphogenesis.
The stiffness of the hair follicle is expected to extend over several orders of magnitude, due to the differentiation of its soft kera. Keratins are best known for providing strength and resilience to cells that form the hair, skin, and nails. Hair keratin pattern in human hair follicles grown in. Hair keratin pattern in human hair follicles grown in vitro. Hair is one of the characteristic features of mammals and has various functions such as protection against external factors. Request pdf keratins of the human hair follicle substantial progress has been made regarding the elucidation of differentiation processes of the human hair. Isolation of intermediate filament assemblies from human. Structure and expression of genes for a class of cysteinerich proteins of the cuticle layers of differentiating wool and hair follicles. The human hair follicle was used here as a model system to show how the local, microscopic network architecture is connected to local mechanical properties in a tridimensional tissue. Keratins are also involved in several other critical cell functions, including cell movement migration, regulation of cell. Stark hj, breitkreutz d, limat a, et al 1987 keratins of the human hair follicle. Aside from hair keratins, other keratin group members include epithelial and hair follicle specific epithelial keratins.
Throughout the keratinization process and hair fibers production, numerous keratins organize into protein filaments to participate in the assembly of the hair shaft within follicle bulbs 1,2,3. In the human genome, the keratin genes are clustered at two different chromosomal sites. Nutrients free fulltext induction of hair keratins. Jurgen stark division of differentiation and carcinogenesis in vitro, institute of biochemistry, german cancer research center, im neuenheimer feld 280, d. Request pdf keratins of the human hair follicle substantial progress has been made regarding the elucidation of differentiation processes of the human hair follicle. While a consensus is rapidly building in support of an autoimmune pathogenesis, there are still several. We have examined the growth capacity of keratinocytes isolated from human scalp hair follicles. Keratins k5, k14, k17, k25, k27, k28, and k75 define a premedulla. Keratins of the human hair follicle request pdf researchgate. The type i hair keratin gene subfamily on chromosome 17q1221 comprises nine genes, which in. It is the key structural material making up hair, nails, feathers, horns, claws, hooves, calluses, and the outer layer of skin among vertebrates.
The last few years have yielded an explosion of more rigorously obtained data on the etiology and pathogenesis of this disorder. Human hair growth in vitro journal of cell science. Hyperproliferative keratins consistently expressed in outer root sheath cells in vivo and in vitro hansjiirgen stark, dirk breitkreutz, alain limat, paul bowden 3, and norbert e. Sections describe the role and fate of hair keratins in the diseased hair follicle, particularly hereditary disorders and hair follicle derived tumors. The hf has a wide range of functions including thermoregulation, physical and immunological protection against external insults, sensory perception, social interactions, and camouflage. Isolation of intermediate filament assemblies from human hair.
The main components of human hair are keratin proteins. Location of stem cells of human hair follicles by clonal. The catalog of human hair keratins journal of biological chemistry. In this study, we used cyclosporine a as a lead compound to identify novel therapeutic targets that. The latter comprise keratins also present in outer and innerroot sheaths and in the companion layer. Hyperproliferative keratins consistently expressed in outer root sheath cells in vivo and in vitro.
Therefore, we investigated the effects of low and high concentrations of biotin on proliferation and differentiation of cultured outer root sheath cells from. Aside from hair keratins, other keratin group members include epithelial and hair folliclespecific epithelial keratins. Intact hair follicles were then removed from the fat using watchmakers forceps. Keratin network modifications lead to the mechanical. Hyperproliferative keratins consistently expressed in outer root sheath cells in vivo and in vitro hans.
Christianoa,b,1 departments of adermatology, bgenetics and development, and csystems biology, columbia university, new york, ny 10032. Cosmetics free fulltext human hair and the impact of. Five million total hair follicles in the adult human, without significant racial or sexual differences scalp has highest density, but declines with age from 15cm 2 at birth to 300500cm 2 in adults for a total of 100,000 follicles. Hyperproliferative keratins consistently expressed in outer root sheath cells in vivo and in vitro article pdf available in differentiation 353. However, it cannot be effectively used to restore hair growth because of its toxic profile. Isolation of the hair follicles was achieved by cutting the follicle at the dermosubcutaneous fat interface using a scalpel blade. Hair keratins are members of the intermediate filament family of proteins, yet are sufficiently divergent from epidermal keratins to warrant separate classification. Wenzel, ralf paus, thyroid hormones directly alter human hair follicle functions.
In the last decades many hair folliclespecific epithelial keratins were discovered, which are built up from a somewhat separate gene subfamily 11,12. The amino acid composition of human hair keratins is typically different from the remaining keratins. Cortical fusi are air spaces of varying sizes found near the root of a mature human hair. Of all the hair keratins, only type ii hair keratin hhb4 and type i hair keratin hha7 could not be detected by iif in terminal scalp hairs see section ii. Intermediate filament proteins resource hair keratins. Mutation of a type ii keratin gene k6a in pachyonychia.
Some of them have extensive growth potential, as they are able to undergo at least doublings. In humans and in animals, biotin deficiency causes pathological changes in the skin and its appendages. Thyroid hormones directly alter human hair follicle functions. All in all, out of the 54 human keratin genes, at least 26 50% are speciwcally expressed in the hair follicle. Hyperproliferativekeratins consistently expressed in outer root sheath cells in vivo and in vitro hans. Like the keratinocytes of glabrous epidermis, most of the colonyforming cells are classified as holoclones or meroclones when analyzed in a clonal assay. Proliferation and differentiation of cultured human. The lower part of the follicles was cut off and extracted for hair keratins as described. Recently, the study of human kap has advanced significantly. Human hair keratins were among the first to be studied but it is only recently that sufficient information has been obtained to gain a basic biologic perspective of these proteins. The majority of the hair keratins remain unlinked to human phenotypes. Author summary hair loss is a common disorder and can lead to psychological distress.
Hyperproliferativekeratins consistently expressed in outer root sheath cells in vivo and in vitro article pdf available in differentiation 353. Keratin also protects epithelial cells from damage or stress. May 07, 2008 thus, there are 28 type i keratin genes 17 epithelial keratins and 11 hair keratins and 26 type ii keratin genes 20 epithelial keratins and 6 hair keratins. Nineteen different keratin genes including hair keratins and hair folliclespecific epithelial keratins have up to now been identified as being.
All in all, out of the 54 human keratin genes, at least 26. The human type ii keratin gene cluster on chromosome. The base of each hair shaft hs resides in a multicellular miniorgan called hair follicle hf that is invaginated under the surface of the skin. Expression of keratin k14 in the epidermis and hair. Also included is a report on the actual state of knowledge concerning the regulation of hair keratin expression.
Comparative genomics analyses of alphakeratins reveal. The expression of hha7 is conspic uously different from that of the other hair keratins in that it does not occur in the large anagen follicles of terminal scalp hairs. The human hair shaft consists of three different layers. Sections describe the role and fate of hair keratins in the diseased hair follicle, particularly hereditary disorders and hair folliclederived tumors. Oct 24, 2017 recent discovery of hair follicle keratin 75 krt75 in enamel raises questions about the function of this protein in enamel and the mechanisms of its secretion. Human anagen hair follicles were isolated by microdissection from human scalp skin.
The most significant difference corresponds to the cysteine residue content 7. Microenvironmental reprogramming by three dimensional. Hair folliclespecific keratin genes consisted of 9 hair folliclespecific epithelial keratin genes k71k75, k25k28 and 17 hair keratins k31k40, k81k86 expressed in hair follicle and hair which could directly affect hair growth. It is also not clear how this protein with a very specific and narrow expression pattern, limited to the inner root sheath of the hair follicle, became associated with enamel. Contains pigment bodies, which contains the melanin hair color and cortical fusi. Combing the genome for the root cause of baldness nature.
To study this problem, we have prepared several mouse monoclonal antibodies that recognize different classes of human hair proteins. A large number of diseases of hair were caused by mutations in hair folliclespecific keratin genes. Whereas hhb4 was found in the filiform tongue papilla fig. Hair keratinassociated proteins kap are a major component of the hair fiber, and play crucial roles in forming a strong hair shaft through a crosslinked network with keratin intermediate filaments kif, which are produced from hair keratins. We have investigated the expression of 52 of the 54 keratins in beard hair medulla. Both growth kinetics and gross morphology of the follicles were found to be comparable to the in vivo situation, and follicles kept growing at a rate of 0. The keratin associated kap proteins that constitute the matrix of the keratin composite of wool. So far, five clusters of human kap genes have been characterized, leading to the. Human hair graying is naturally reversible and linked to. In this catalog, hhb5 showed up as a series of isoelectric variants, well separated from a lower, more acidic, and complex protein streak containing isoelectric variants of hair keratins hhb1, hhb2, hhb3, and. All in all, out of the 54 human keratin genes, at least 26 50% are specifically expressed in the hair follicle. Hair is a derivative of the epidermis and consists of two distinct parts. Hair keratins have relatively high sulfur content in their head and tail globular domains, and are further reinforced by a continuous phase of highly crosslinked matrix proteins referred to as keratinassociated proteins kaps. Human hair keratins journal of investigative dermatology.
Similarly, the keratinization processduring which keratin is formed and its. Basics hair has little remaining physiologic importance, but great psychological importance. The onset of hair graying varies between individuals based on genetic and other biobehavioral factors, but most people experience depigmentation of a progressively large number of hair shafts hs from their third decade onward, known as achromotrichia or canities6. The molecular anatomy of mouse skin during hair growth and.
Secondly, hard keratins, at least those of wool and human hair, are al most totally insoluble under conditions that solubilize soft keratins e. They differ from the canonical epithelial keratins by considerably higher sulphur content in their non. Expression of keratin k14 in the epidermis and hair follicle. High doses of biotin may also have beneficial effects on skin, hair and fingernails in humans and animals with normal biotin status. Onedimensional sodium dodecyl sulfatepolyacrylamide gel electrophoresis sdspage. Keratins in human hair a thesis submitted to the university of manchester for the degree of doctor of philosophy ph. The major hair proteins, keratins and keratin associated proteins kaps, have been shown to be expressed specifically in the respective layers of the hair shaft. In line with aa affecting the hair follicle and nails but not the epidermis, there are several keratins that are expressed exclusively in hair follicles and nails 24, 25, 33. Keywords follicular morphogenesis 4 hair follicle 4 hair life cycle 4 keratin. A human hair follicle in vitro culture model in which isolated hair follicles were maintained free. Hair and follicle morphology in utero, type and distribution of each hair follicle over the entire body are determined. Cooption of hair follicle keratins into amelogenesis is. Although numerous hair proteins have been studied biochemically and many have been sequenced, relatively little is known about their in situ distribution and differential expression in the hair follicle.
Nina van beek, eniko bodo, arno kromminga, erzsebet gaspar, katja meyer, michal a. We found that not only 12 hair keratins but, unexpectedly, also 12 epithelial keratins are potentially expressed in medulla cells. Pdf the human type ii hair keratin subfamily consists of six individual members. Identifying novel strategies for treating human hair loss. Alopecia areata is a common disfiguring hair loss disorder that primarily affects the hair follicle as it enters the prolonged growth phase called anagen. Since selected keratins are now understood to exert important regulatory functions beyond mechanical stability. Their colocalization in upper cortical and cuticle cells of the human hair follicle and. Studies on the proteome of human hair identification of.
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