A Novel Human Type II Cytokeratin, K6hf, Specifically Expressed in the Companion Layer of the Hair Follicle

Abstract

In an attempt to identify new members of the human type II hair keratin family by means of 3'- and 5'-RACE methods and cDNA from anagen hair follicles, we detected a sequence that encoded a hitherto unknown type II cytokeratin. The novel cytokeratin comprises 251 amino acids and exhibits the highest sequence homology with K5. Comparative one- and two-dimensional western blots of keratins from anagen hair bulbs, containing or not containing the outer and inner root sheaths (ORS/IRS), and from footsole epidermis with an antibody against the new cytokeratin, revealed its comigration with K6 and its expression in the ORS/IRS complex. We have therefore named the new cytokeratin K6hf, to distinguish it from the various K6 isoforms and to indicate its expression in the hair follicle. Both in situ hybridization with a K6hf-specific cRNA probe and indirect immunofluorescence with the K6hf antibody showed that K6hf is exclusively expressed in the so-called "companion layer" of the hair follicle, a single layered band of flat and vertically oriented cells between the cuboidal ORS cells and the IRS that stretches from the lowermost bulb region to the isthmus of the follicle. Concomitant K17 and K16 expression studies showed that besides suprabasal ORS cells, these cytokeratins are sequentially expressed subsequent to K6hf in companion cells above the hair bulb. Our study confirms the view of a vertically oriented companion layer differentiation. The clearly delayed K17 and K16 expression relative to that of K6hf in companion cells most probably excludes these keratins as possible type I partners of K6hf and suggests the existence of a still unknown type I partner of its own. Thus, not only morphologically but also biochemically, the companion layer is different from the ORS and can therefore be regarded as an independent histologic compartment of the hair follicle.

The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle

“…7D). Moreover, the cytokeratin K6hf, which is specifically expressed in the companion cell layer of wild-type follicles (Winter et al 1998), was detected throughout the IRS as well as in the cortex of Cutl1 Z/Z follicles (Fig. 7E).…”

“…In contrast, however, the companion cells are in intimate contact with cells of Henlé's layer through desmosomes and gap junctions and therefore may form a slippage plane to allow the growing hair fiber to move along the ORS (Rothnagel and Roop 1995). Moreover, the elongated and vertically oriented companion cells are also morphologically and biochemically distinct from the cuboidal ORS cells, which has led to the hypothesis that the companion cells constitute an independent histological compartment of the hair follicle (Rothnagel and Roop 1995;Winter et al 1998). The coexpression of Cutl1 in the IRS and companion cells now strongly argues that the companion cells constitute the fourth and outermost layer of the IRS.…”

Multi-potentiality of a new immortalized epithelial stem cell line derived from human hair follicles

“…Our results indicate that primary skin stem cells as well as the Tel-E6E7 cell line are able to differentiate into epidermal, hair follicle and sebaceous lineages. For in vitro hair differentiation, expression of Keratin 6 hair follicle (K6hf), which is specifically expressed in the companion layer of the hair follicle (Winter et al 1998), increased after co-culture with dermal papilla cells for 2 days ( Figure 4A). We previously showed that this induction of hair differentiation depended on active Wnt-β-catenin signaling (Roh et al 2004).…”

Hair follicle differentiation and regulation.

“…The alternative is for the layer to move with the IRS as that layer differentiates with the growing hair. Families of K6 proteins together with K16 (Rothnagel and Roop, 1995, Takahashi et al, 1995, Winter et al, 1998) are expressed in the companion layer and presumably they correspond to the keratin IFs seen in the cells.…”