Rat hair follicle growth in vitro

Philpott, Michael P.; Green, M.R.; Kealey, Terence

doi:10.1111/j.1365-2133.1992.tb14873.x

Cited by 178 publications

(231 citation statements)

References 22 publications

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“…Then, 4 mm punches were set in the skin surrounding each 2 mm hole to obtain 'punch within a punch' skin samples (Moll et al, 1998). Samples were frozen immediately for analysis (day 0) or transferred to six-well plates containing Williams E culture medium supplemented with insulin and hydrocortisone (Philpott et al, 1990;. Each well contained two skin punches in 3 ml medium.…”

Section: Human Skin Biopsies and Wound Healing Organ Culture Assaymentioning

confidence: 99%

Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury

et al. 2011

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SUMMARYThe Lhx2 transcription factor plays essential roles in morphogenesis and patterning of ectodermal derivatives as well as in controlling stem cell activity. Here, we show that during murine skin morphogenesis, Lhx2 is expressed in the hair follicle (HF) buds, whereas in postnatal telogen HFs Lhx2 + cells reside in the stem cell-enriched epithelial compartments (bulge, secondary hair germ) and co-express selected stem cell markers (Sox9, Tcf4 and Lgr5). Remarkably, Lhx2+ cells represent the vast majority of cells in the bulge and secondary hair germ that proliferate in response to skin injury. This is functionally important, as wound reepithelization is significantly retarded in heterozygous Lhx2 knockout (+/-) mice, whereas anagen onset in the HFs located closely to the wound is accelerated compared with wild-type mice. Cell proliferation in the bulge and the number of Sox9 + and Tcf4 + cells in the HFs closely adjacent to the wound in Lhx2 +/-mice are decreased in comparison with wild-type controls, whereas expression of Lgr5 and cell proliferation in the secondary hair germ are increased. Furthermore, acceleration of wound-induced anagen development in Lhx2 +/-mice is inhibited by administration of Lgr5 siRNA. Finally, Chip-on-chip/ChIP-qPCR and reporter assay analyses identified Sox9, Tcf4 and Lgr5 as direct Lhx2 targets in keratinocytes. These data strongly suggest that Lhx2 positively regulates Sox9 and Tcf4 in the bulge cells, and promotes wound re-epithelization, whereas it simultaneously negatively regulates Lgr5 in the secondary hair germ and inhibits HF cycling. Thus, Lhx2 operates as an important regulator of epithelial stem cell activity in the skin response to injury.

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Section: Human Skin Biopsies and Wound Healing Organ Culture Assaymentioning

confidence: 99%

Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury

et al. 2011

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“…Maximally growing (i.e. anagen VI) hair follicles from normal human scalp skin were isolated, micro-dissected and organ-cultured (Philpott et al, 1990; Magerl et al, were counted and the ratio between both numbers was determined (ctrl, n=10; menadione, n=9; KGF, n=11; KGF+menadione, n=12; n, number of hair follicles). Means ± s.e.m.…”

Section: Kgf Is Cytoprotective For Human Keratinocytes In Vitromentioning

confidence: 99%

Keratinocyte growth factor protects epidermis and hair follicles from cell death induced by UV irradiation, chemotherapeutic or cytotoxic agents

Braun

Krampert²,

Bodó

et al. 2006

Journal of Cell Science

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Owing to its potent cytoprotective properties for epithelial cells, keratinocyte growth factor (KGF) is successfully used for the treatment of chemotherapy- and radiotherapy-induced oral mucositis in cancer patients. It is therefore of major interest to determine possible clinical applications of KGF in other organs and in different stress situations and to unravel common and organ-specific mechanisms of KGF action. Here we show that KGF protects human keratinocytes from the toxicity of xenobiotics with electrophilic and oxidative properties and reduces the cell death induced by UV irradiation. In contrast to other cell types, cytoprotection of keratinocytes by KGF is not a direct anti-apoptotic effect but requires de novo protein synthesis. The in vitro findings are clinically relevant because KGF protected keratinocytes in organ-cultured human scalp hair follicles from the toxicity of the xenobiotic menadione. Moreover, injection of KGF into murine back skin markedly reduced cell death in the epidermis after UVB irradiation. This activity is dependent on FGF receptor signaling because it was abrogated in transgenic mice expressing a dominant-negative FGF receptor mutant in keratinocytes. Taken together, our results encourage the use of KGF for skin protection from chemical and physical insults.

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“…In mouse skin, exogenous introduction of FGF5 by s.c. injection of recombinant proteins has previously been shown to induce premature entry into catagen, whereas FGF5S introduction can antagonize this effect (24), presumably by competitively binding the FGF5 receptor, FGFR1 (11). To assess the effect of FGF5 on the human hair cycle, we used the well-established organ culture model (25) for hair fiber elongation and grew microdissected human scalp hair follicles in the presence of recombinant FGF5 (Fig. 4C).…”

Section: Identification Of Causative Mutations In Fibroblast Growth Fmentioning

confidence: 99%

FGF5 is a crucial regulator of hair length in humans

Higgins¹,

Petukhova²,

Harel³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

141

118

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Mechanisms that regulate the growth of eyelashes have remained obscure. We ascertained two families from Pakistan who presented with familial trichomegaly, or extreme eyelash growth. Using a combination of whole exome sequencing and homozygosity mapping, we identified distinct pathogenic mutations within fibroblast growth factor 5 (FGF5) that underlie the disorder. Subsequent sequencing of this gene in several additional trichomegaly families identified an additional mutation in FGF5. We further demonstrated that hair fibers from forearms of these patients were significantly longer than hairs from control individuals, with an increased proportion in the growth phase, anagen. Using hair follicle organ cultures, we show that FGF5 induces regression of the human hair follicle. We have identified FGF5 as a crucial regulator of hair growth in humans for the first time, to our knowledge, and uncovered a therapeutic target to selectively regulate eyelash growth.hair cycling | catagen | next-generation sequencing | consanguineous families

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Rat hair follicle growth in vitro

Cited by 178 publications

References 22 publications

Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury

Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury

Keratinocyte growth factor protects epidermis and hair follicles from cell death induced by UV irradiation, chemotherapeutic or cytotoxic agents

FGF5 is a crucial regulator of hair length in humans

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