Reconstitution of Hair Follicle Development In Vivo: Determination of Follicle Formation, Hair Growth, and Hair Quality by Dermal Cells

Weinberg, Wendy C.; Goodman, Linda; George, Carmen; Morgan, David L.; Ledbetter, Steve; Yuspa, Stuart H.; Lichti, Ulrike

doi:10.1111/1523-1747.ep12468971

Cited by 201 publications

(179 citation statements)

References 18 publications

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“…Next, we checked if cKO RU hfSCs retained multipotency characteristics and regenerative potential in vivo by performing chamber graft experiments (Fig. S2F) (26). Cultured YFP+ hfSCs from both cKO RU and CON RU were mixed with freshly isolated newborn dermal fibroblasts and engrafted into athymic mice ( Fig.…”

Section: Use Of a Genetic Model To Visualize Hfsc Molecular Dynamics mentioning

confidence: 99%

Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation

Kandyba

Leung

Chen

et al. 2013

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

159

214

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Hair follicles facilitate the study of stem cell behavior because stem cells in progressive activation stages, ordered within the follicle architecture, are capable of cyclic regeneration. To study the gene network governing the homeostasis of hair bulge stem cells, we developed a Keratin 15-driven genetic model to directly perturb molecular signaling in the stem cells. We visualize the behavior of these modified stem cells, evaluating their hair-regenerating ability and profile their molecular expression. Bone morphogenetic protein (BMP)-inactivated stem cells exhibit molecular profiles resembling those of hair germs, yet still possess multipotentiality in vivo. These cells also exhibit up-regulation of Wnt7a, Wnt7b, and Wnt16 ligands and Frizzled (Fzd) 10 receptor. We demonstrate direct transcriptional modulation of the Wnt7a promoter. These results highlight a previously unknown intra-stem cell antagonistic competition, between BMP and Wnt signaling, to balance stem cell activity. Reduced BMP signaling and increased Wnt signaling tilts each stem cell toward a hair germ fate and, vice versa, based on a continuous scale dependent on the ratio of BMP/Wnt activity. This work reveals one more hierarchical layer regulating stem cell homeostasis beneath the stem cell-dermal papilla-based epithelial-mesenchymal interaction layer and the hair follicle-intradermal adipocyte-based tissue interaction layer. Although hierarchical layers are all based on BMP/Wnt signaling, the multilayered control ensures that all information is taken into consideration and allows hair stem cells to sum up the total activators/inhibitors involved in making the decision of activation.hair follicle stem cells | β-catenin | BMPR1A

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Section: Use Of a Genetic Model To Visualize Hfsc Molecular Dynamics mentioning

confidence: 99%

Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation

Kandyba

Leung

Chen

et al. 2013

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

159

214

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“…The keratinocyte-specific pattern of whn expression suggested that the functional defect in nude mouse hair development lies in the epithelial cells. We tested this possibility using a recently developed hair reconstitution grafting assay Weinberg et al 1993). Hair buds were isolated from either wild-type Swiss (whn + / +) or nude (Swiss whn / -) newborn mouse pups and grafted with rat dermal papilla cells onto nude mice (Fig.…”

Section: Epithelial-specific Expression Of Whn Correlates With An Intmentioning

confidence: 99%

“…The hair reconstitution assays were performed using freshly prepared hair buds (2.5 skin equivalents/graft), rat dermal papilla cells (8xl0a/graft), and Swiss 3T3-J2 fibroblasts (2×106/ graft; kindly provided by Dr. H. Green, Harvard Medical School, Boston, MA) as described previously Weinberg et al 1993). Prior to grafting, hair buds were combined with dermal papilla cells and Swiss 3T3 fibroblasts, and subjected to centrifugation (1000g, 5 rain).…”

Section: Hair Reconstitution Grafting Assaymentioning

confidence: 99%

The product of the mouse nude locus, Whn, regulates the balance between epithelial cell growth and differentiation.

Brissette¹,

Li²,

Kamimura³

et al. 1996

Genes Dev.

144

141

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Mutations in the winged-helix nude (whn) gene result in the nude mouse and rat phenotypes. The pleiotropic nude phenotype which affects the hair, skin, and thymus suggests that whn plays a pivotal role in the development and/or maintenance of these organs. However, little is known about whn function in these organs. We show here that in skin whn is specifically expressed in epithelial cells and not the mesenchymal cells, and using a hair reconstitution assay, we demonstrate that the abnormal nude mouse hair development is attributable to a functional defect of the epithelial cells. Examination of nude mouse primary keratinocytes in culture revealed that these cells have an increased propensity to differentiate in an abnormal fashion, even under conditions that promote proliferation. Furthermore, nude mouse keratinocytes displayed a 100-fold increased sensitivity to the growth-inhibitory/differentiation effects of the phorbol ester TPA. In parallel with these findings, we directly show that whn functions as a transcription factor that can specifically suppress expression of differentiation/TPA-responsive genes. The region of Whn responsible for these effects was mapped to the carboxy-terminal transactivating domain. These results establish whn as a key regulatory factor involved in maintaining the balance between keratinocyte growth and differentiation. The general implications of these findings for an epithelial self-renewal model will be discussed.[Key Words: Whn; transcriptional factor; nude mouse; keratinocytes] Received June 3, 1996; revised version accepted July 12, 1996.The skin and its appendage, the hair follicle, provide excellent models for the study of the complex control mechanisms involved in organ morphogenesis and homeostasis. The formation and maintenance of the epidermis and the hair follicle, both self-renewing struc-

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“…15,16 Adult mouse bone marrow cells gave rise to epidermal keratinocytes, follicular epithelial cells, sebaceous gland cells, dendritic cells, and endothelial cells within 3 weeks after transplantation.…”

mentioning

confidence: 99%

Participation of Adult Mouse Bone Marrow Cells in Reconstitution of Skin

Kataoka

Medina

Kageyama

et al. 2003

The American Journal of Pathology

122

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Results of recent studies have indicated that bone marrow cells can differentiate into various cells of ectodermal, mesodermal, and endodermal origins when transplanted into the body. However, the problems associated with those experiments such as the long latent period, rareness of the event, and difficulty in controlling the processes have hampered detailed mechanistic studies. In the present study, we examined the potency of mouse bone marrow cells to differentiate into cells comprising skin tissues using a skin reconstitution assay. Bone marrow cells from adult green fluorescent protein (GFP)-transgenic mice were transplanted in a mixture of embryonic mouse skin cells (17.5 days post-coitus) onto skin defects made on the backs of nude mice. Within 3 weeks, fully differentiated skin with hair was reconstituted. GFP-positive cells were found in the epidermis, hair follicles, sebaceous glands, and dermis. The localization and morphology of the cells, results of immunohistochemistry, and results of specific staining confirmed that the bone marrow cells had differentiated into epidermal keratinocytes, sebaceous gland cells, follicular epithelial cells, dendritic cells, and endothelial cells under the present conditions. These results indicate that this system is suitable for molecular and cellular mechanistic studies on differentiation of stem cells to various epidermal and dermal cells.

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Reconstitution of Hair Follicle Development In Vivo: Determination of Follicle Formation, Hair Growth, and Hair Quality by Dermal Cells

Cited by 201 publications

References 18 publications

Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation

Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation

The product of the mouse nude locus, Whn, regulates the balance between epithelial cell growth and differentiation.

Participation of Adult Mouse Bone Marrow Cells in Reconstitution of Skin

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