In search of the “hair cycle clock”: a guided tour

Paus, Ralf; Foitzik, Kerstin

doi:10.1111/j.1432-0436.2004.07209004.x

Cited by 283 publications

(336 citation statements)

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“…Many growth factors have been reported as derived from DPCs [25,[41][42][43]. Some of these factors might contribute to the higher number of epidermis layers and the stem cell population present in the DPC composite skin constructs in vitro.…”

Section: Discussionmentioning

confidence: 99%

Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

Leirós

Kusinsky

Drago³

et al. 2014

Stem Cells Translational Medicine

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Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and might contribute to the understanding of skin regeneration. The use of dermal papilla cells (DPCs) as a dermal component in a permanent composite skin with human hair follicle stem cells (HFSCs) was evaluated by studying the tissue-engineered skin architecture, stem cell persistence, hair regeneration, and graft-take in nude mice. A porcine acellular dermal matrix was seeded with HFSCs alone and with HFSCs plus human DPCs or dermal fibroblasts (DFs). In vitro, the presence of DPCs induced a more regular and multilayered stratified epidermis with more basal p63-positive cells and invaginations. The DPC-containing constructs more accurately mimicked the skin architecture by properly stratifying the differentiating HFSCs and developing a well-ordered epithelia that contributed to more closely recapitulate an artificial human skin. This acellular dermal matrix previously repopulated in vitro with HFSCs and DFs or DPCs as the dermal component was grafted in nude mice. The presence of DPCs in the composite substitute not only favored early neovascularization, good assimilation and remodeling after grafting but also contributed to the neovascular network maturation, which might reduce the inflammation process, resulting in a better healing process, with less scarring and wound contraction. Interestingly, only DPC-containing constructs showed embryonic hair bud-like structures with cells of human origin, presence of precursor epithelial cells, and expression of a hair differentiation marker. Although preliminary, these findings have demonstrated the importance of the presence of DPCs for proper skin repair.

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Section: Discussionmentioning

confidence: 99%

Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

Leirós

Kusinsky

Drago³

et al. 2014

Stem Cells Translational Medicine

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“…For example, vasoactive intestinal peptide receptor (Vip receptor) is expressed in the murine bulge region during anagen V, but disappears in all other phases of the murine hair cycle (Wollina et al 1995). Though it Page 9 of 38 A c c e p t e d M a n u s c r i p t 9 is conceivable that this neuropeptide receptor plays a role in hair cycle-associated changes in HFeSC chronobiology (Paus and Foitzik, 2004), the significance of VIPinduced signalling for HFeSC functions has not yet been followed up and thus remains completely obscure.…”

Section: Immunohistological Patterns Of Hair Follicle Located (Neuro-mentioning

confidence: 99%

“…A c c e p t e d M a n u s c r i p t Botchkarev et al, 1999Peters et al, 1999Souza et al, 2006 Alonso and Fuchs, 2006 Aminik et al, 2007Paus and Foitzik, 2004Schlake, 2005aSchlake, 2005bStenn and Paus, 2001 Weger and Schlake,…”

Section: Acknowledgementsmentioning

confidence: 99%

(Neuro-)endocrinology of epithelial hair follicle stem cells

Paus

Arck

Tiede

2008

Molecular and Cellular Endocrinology

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The hair follicle is a repository of different types of somatic stem cells. However, even though the hair follicle is both a prominent target organ and a potent, non-classical site of production and/or metabolism of numerous polypetide-and steroid hormones, neuropeptides, neurotransmitters and neurotrophins, the (neuro-) endocrine controls of hair follicle epithelial stem cell (HFeSC) biology remain to be systematically explored.Focussing on HFeSCs, we attempt here to offer a "roadmap through terra incognita" by listing key open questions, by exploring endocrinologically relevant HFeSC gene profiling and mouse genomics data, and by sketching several clinically relevant pathways via which systemic and/or locally generated (neuro-)endocrine signals might impact on HFeSC. Exemplarily, we discuss e.g. the potential roles of glucocorticoid and vitamin D receptors, the hairless gene product, thymic hormones, bone morphogenic proteins (BMPs) and their antagonists, and Skg-3 in HFeSC biology. Furthermore, we elaborate on the potential role of nerve growth factor (NGF) and substance P-dependent neurogenic inflammation in HFeSC damage, and explore how neuroendocrine signals may influence the balance between maintenance and destruction of hair follicle immune privilege, which protects these stem cells and their progeny. These considerations call for a concerted research effort to dissect the (neuro)-endocrinology of HFeSCs much more systematically than before. The hair follicle (HF) and its special, associated mesenchyme (i.e. the connective tissue sheath, CTS) are repositories of different types of somatic stem cells (epithelial, mesenchymal, neural, mesenchymal) (Cotsarelis, 2006; Kruse et al., 2006;Millar, 2005;Ohyama et al., 2006;Tiede et al. 2007;Waters et al., 2007;Yu et al., 2006). These HFassociated stem cell populations are critical for HF development and function, including HF pigmentation (Nishimura et al., 2002(Nishimura et al., , 2005Sarin and Artandi, 2007). Fig. 1 shows several important, recognized hair follicle-associated stem cell populations and their bestcharacterized location(s) in the pilosebaceous unit, though it must be kept in mind that the indicated ones are unlikely to be the only stem cell population associated with mammalian skin appendages (Tiede et al. 2007). Clinical importance of hair follicle stem cellsHair follicle epithelial stem cells (HFeSCs) are clinically important, since they can be key targets for pathological processes, such as an autoaggressive inflammatory cell attack on HFeSC, e.g. in lupus erythematosus or lichen planopilaris, where the destruction of bulge HFeSCs (see Fig.1) abolishes the hair follicle's capacity to cycle and to rhythmically regenerate itself, leading to scarring alopecia (Cotsarelis, 2006;Hiroi et al., 2006;Mobini et al., 2005;Paus, 2006). Likewise, a gradual loss of HF melanocyte stem cells may exhaust the HF pigmentary unit's capacity to generate itself and to produce melanin and thus likely plays a key role in hair graying (Commo et al., 2004;...

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“…Hair follicles go through regenerative cycles: they cycle through growth (anagen), regression (catagen), hair shaft shedding (exogen) and resting phases (telogen) (Paus and Cotsarelis, 1999;Paus and Foitzik 2004;Stenn & Paus 2001). Visualizing hair waves is facilitated by hair cycle dependent changes in integument pigmentation and timed hair loss in nude mice (Militzer, 2001;Suzuki et al, 2003), Msx2 null mice (Ma et al, 2003), calcineurin B1 (Mammucari et al, 2005), etc.…”

Section: Traveling Wavementioning

confidence: 99%

Distinct mechanisms underlie pattern formation in the skin and skin appendages

Widelitz

Baker²,

Plikus

et al. 2006

Birth Defects Research Pt C

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SummaryPatterns form with the break of homogeneity, leading to the emergence of new structure or arrangement. There are different physiological and pathological mechanisms which lead to the formation of patterns. Here we first introduce the basics of pattern formation and their possible biological basis. We then discuss different categories of skin patterns and their potential underlying molecular mechanisms. Some patterns, such as the lines of Blaschko and naevus, are based on cell lineage and genetic mosaicism. Other patterns, such as regional specific skin appendages, can be set by distinct combinatorial molecular codes, which in turn may be set by morphogenetic gradients. There are also some patterns, such as the arrangement of hair follicles (hair whorls) and fingerprints, which involve genetics as well as stochastic epigenetic events based on physical-chemical principles. Many appendage primordia are laid out in developmental waves. In the adult, some patterns, such as those involving cycling hair follicles, may appear as traveling waves in mutant mice. Since skin appendages can renew themselves in regeneration, their size and shape can still change in the adult via regulation by hormones and the environment. Some lesion patterns are based on pathological changes involving the above processes and can be used as diagnostic criteria in medicine. Understanding the different mechanisms which lead to patterns on the skin will help us appreciate their full significance in morphogenesis and medical research. Much remains to be learned about complex pattern formation, a level between molecular biology and organism phenotypes.

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In search of the “hair cycle clock”: a guided tour

Cited by 283 publications

References 182 publications

Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

(Neuro-)endocrinology of epithelial hair follicle stem cells

Distinct mechanisms underlie pattern formation in the skin and skin appendages

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