Hair follicle stem cells: Walking the maze

Tiede, Stephan; Kloepper, Jennifer E.; Bodó, Enikő; Tiwari, Sanjay; Kruse, Charli; Paus, Ralf

doi:10.1016/j.ejcb.2007.03.006

Cited by 165 publications

(158 citation statements)

References 171 publications

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“…This adds to many other hematopoietic factors that are expressed in the HFs: CD34, but also Tcf-3/Lef-1, NFATC1, S100A4, LTBP1, b1-integrin and so on. (Tiede et al, 2007). We believe that this study may contribute to a better understanding of the cellular mechanisms underlying the physiology of a population of adult stem cells and to the opening of a novel field of study for TCL1 function.…”

Section: Discussionmentioning

confidence: 85%

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

et al. 2009

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Overexpression of the TCL1 gene family plays a role in the onset of T-cell leukemias in mice and in humans. The Tcl1 gene is tightly regulated during early embryogenesis in which it participates in embryonic stem (ES)-cells proliferation and during lymphoid differentiation. Here, we provide evidences that Tcl1 is also important in mouse hair follicle (HF) and skin homeostasis. We found that Tcl1 À/À adult mice exhibit hair loss, leading to alopecia with extensive skin lesions. By analysing Tcl1 expression in the wild-type (wt) skin through different stages of hair differentiation, we observe high levels in the secondary hair germ (HG) cells and hair bulges, during early anagen and catagen-telogen transition phases. The loss of Tcl1 does not result in apparent skin morphological defects during embryonic development and at birth, but its absence causes a reduction of proliferation in anagen HFs. Importantly, we show the that absence of Tcl1 induces a significant loss of the stem-cell marker CD34 (but not a6-integrin) expression in the bulge cells, which is necessary to maintain stem-cell characteristics. Therefore, our findings indicate that Tcl1 gene(s) might have important roles in hair formation, by its involvement in cycling and self-renewal of transient amplifying (TA) and stem-cell (SC) populations.

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Section: Discussionmentioning

confidence: 85%

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

et al. 2009

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“…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). …”

Section: The Hair Follicle As a Somatic Stem Cell Repositorymentioning

confidence: 99%

“…1) of both murine and human HFs that were classified as "HF epithelial stem cells" (HFeSC) on the basis of GFP (green fluorescent protein)-visualized cytokeratin 15 promoter activity for targeting epithelial SCs in the HF bulge (Liu et al, 2003;Ito et al, 2005). Morris et al, 2004;Ohyama et al, 2006;Tiede et al, 2007 andTumbar et al, 2004, have provided particularly valuable pointers to endocrine controls of this population of HFeSCs (Tables 1 and 2). …”

Section: Pointers From Hfesc Gene Profiling Studiesmentioning

confidence: 99%

“…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).…”

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confidence: 99%

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(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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“…14 The present study points to the possible existence of yet another category of players in the development of cutaneous neurofibromas: multipotent NF1 ϩ/Ϫ precursor cells that can give rise to some of the different cell types found in neurofibromas. Our previous histological analyses of apparently normal skin from patients with NF1 revealed minute neurofibromas, presumably in the early stages of development, in the immediate vicinity of the hair follicular apparatus 15 and the finding that hair follicles, together with their adjacent tissue, have been shown to serve as reservoirs of multipotent progenitor cell populations 16 led us to study the potential association of hair root with cutaneous neurofibromas. This concept is further supported by the clinical observation that cutaneous neurofibromas are found only rarely in densely innervated areas devoid of hair, such as the fingertips and lips, whereas less densely innervated areas, such as the skin of the back, frequently host numerous tumors.…”

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confidence: 99%

The Development of Cutaneous Neurofibromas

Jouhilahti

Peltonen

Callens

et al. 2011

The American Journal of Pathology

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Cutaneous neurofibromas are the hallmarks of neurofibromatosis type 1 (NF1). They are composed of multiple cell types, and traditionally they are believed to arise from small nerve tributaries of the skin. A key finding in the context of this view has been that subpopulations of tumor Schwann cells harbor biallelic inactivation of the NF1 gene (NF1 ؊/؊ ). In the present study, our aim was to clarify further the pathogenesis of cutaneous neurofibromas. First, we detected cells expressing multipotency-associated biomarkers in cutaneous neurofibromas. Second, we developed a method for isolating and expanding multipotent neurofibroma-derived precursor cells ( Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene that encodes the tumor suppressor protein neurofibromin, an inactivator of Ras. Clinical diagnosis of the disease is based on the presence of café-au-lait macules, axillary freckling, hamartomas of the iris (Lisch nodules), optic pathway gliomas, distinctive osseous lesions such as sphenoid wing dysplasia or pseudarthrosis, and neurofibromas. 1 Neurofibromas can be classified according to their anatomical location: cutaneous, subcutaneous, intraneural, and plexiform. 2 Plexiform neurofibromas are congenital tumor masses involving nerve trunks and often extend to the skin, whereas cutaneous neurofibromas are not detectable at birth and usually appear during adolescence.Histologically, neurofibromas are mixed tumors consisting of cells with divergent differentiation characteristics. The use of traditional histological stains, as well as immunohistochemistry with a variety of biomarkers and electron microscopy, has been taken as proof for the involvement of Schwann cells, perineurial cells, and fibroblasts. 3-5 Neurofibromas also contain numerous mast cells and axonal processes, all of which are embedded in an abundant collagenous extracellular matrix. 4,6 Unlike plexiform neurofibromas, which carry a risk for malignant transformation and may form tumor masses of several kilograms, cutaneous neurofibromas invariably retain their benign phenotype. Their neoplastic cells never undergo malignant transformation and the tumor diameter usually varies from millimeters to 2 cm, rarely exceeding 3 cm.In light of previous reports and the current study, a feasible explanation for neurofibroma development involves a biallelic inactivation of the NF1 gene. 7,8 This inactivation has been detected in cultured cells displaying characteristics typical of Schwann cells, including a bipolar morphology and the expression of S100 protein.Previous studies have observed diploinsufficiency in 29 of 29 cutaneous neurofibromas in which two separate mutations were found in 26 of 29 tumors and loss of heterozygosity was found in 3 of 29 7 It should be noted that each of the second mutations was unique.

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Hair follicle stem cells: Walking the maze

Cited by 165 publications

References 171 publications

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

(Neuro-)endocrinology of epithelial hair follicle stem cells

The Development of Cutaneous Neurofibromas

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