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Targeted Expression of GFP in the Hair Follicle Using Ex Vivo Viral Transduction (video)

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• CUSTOMIZED CONTRACT RESEARCH AVAILABLE AT ANTICANCER INC.

Topical selective delivery of liposome-lacZ gene to hair follicle of mice

Lingna Li and Robert M. Hoffman: The feasibility of targeted selective gene therapy of the hair follicle. Nature Medicine, 1, 705-706, 1995

_{Blue color indicates lac-Z gene expression in the matrix cells of hair follicle bulb, magnification: a)  400X, b) 1000X} 

Hair shafts genetically modified with GFP growing in mice

SOURCE: Proceedings of the National Academy of Sciences 2002;10.1073/pnas.192453799./Saito, N., Zhao, M., Li.L., Baranov, E., Yang, M., Ohta, Y., Katsuoka, K., Penman, S., and Hoffman R.M. High efficiency genetic modification of hair follicles and growing hair shafts. Proc. Natl. Acad. Sci USA  99, 1310-1314, 2002.

_{IN VITRO HISTOCLTURE HAIR GROWTH ASSAY}

Hair growth with progressing pigment production from anagen-induced C57 Bl-6 mouse skin 

_{Lingna Li et al. Skin histoculture assay for studying the hair cycle. In Vitro Cell. Dev. Biol., 28A:695-698, 1992}

_{Lingna Li et al. Hair shaft elongation, follicle growth, and spontaneous regression in long-term, gelatin sponge-supported histoculture of human scalp skin. Proc. Natl. Acad. Sci. USA Vol. 89, pp.8764-8768, 1992}

SCREEN FOR: Hair Growth Stimulators and Inhibitors, Inhibitors of Chemotherpay Induced Alopecia, Hair Pigment Modifier, Acne Inhibitors - CUSTOMIZED CONTRACT RESEARCH AVAILABLE AT ANTICANCER INC.

Hair-brain connection: Expression of neural stem cell marker nestin found in hair follicle stem cells. 

Li, L., Mignone, J., Yang. M., Matic, M., Penman, S., Enikolopov, G. Nestin Expression in hair follicle sheath progenitor cells. Proc. Natl. Acad. Sci. USA 100(17), 9958-9961, 2003. [PDF]

Transgenic mice with nestin-driven green fluorescent protein (GFP) were found to have nestin expressed in hair follicle stem cells and the developing hair follicle. 

Fig. 1 Nestin-GFP expression in hair follicle stem cells during hair cycle

Nestin-expressing hair follicle stem cells visualized forming the hair follicle by GFP fluorescence.

Fig. 2 Nestin-GFP-expressing stem cells in telogen hair follicle

a1: Low magnification (100X) fluorescence microscopy image shows the ring of bulge nestin-GFP-expressing stem cells (small white box)

a2: High magnification (400X) confocal microscopy image shows ring of nestin-GFP-expressing stem cells in telogen hair follicle similar to that shown in a1 (large white box) 

a3: Higher magnification (1600X) fluorescence microscopy image shows two individual nestin-GFP-expressing stem cells in telogen hair follicle similar to those shown in (a2) (red box). Red arrows indicate the cell body and red arrowheads show the multiple dendritic structure of each cell. 

Fig. 3 Nestin-GFP expressing stem cells forming nascent hair follicle.

Fig. 4A. Co-localization of GFP, nestin and keratin 5/8 & 15 in hair follicle bulge stem cells and outer root sheath cells determined by immunohistochemical staining.

a: Confocal image of nestin expressing hair follicle stem cells (red arrows) forming nascent anagen hair follicle (white arrow). 
b-g: Immunohistochemical stained sections of hair follicles:
                b: Nestin antibody (red arrow) indicating expression in hair follicle stem cells and nascent hair follicle (white arrow)
                c, d: GFP antibody indicating GFP expression in hair follicle stem cells (red stain). Keratin antibody indicating keratin expression 

                        in hair follicle stem cells (brown     stain). Black arrows indicate co-localization keratin and GFP.
                e-g: Serial sections of hair follicle (green arrows indicate GFP expression; red arrows indicate keratin 5/8 expression and blue arrows indicate nestin expression) 

Fig. 4B Colocalization of nestin-GFP and keratin-15 in telogen hair follicle stem cells. 

a: Fluorescence microscopy of frozen section of bulge area of telogen hair follicle of nestin-GFP transgenic mouse counterstained with PI (propidium iodide). Note the nestin-GFP expressing hair follicle stem cells are marked with white arrows.  Magnification 400X.

b: Serial section of (a) was immunohistochemical stained with Keratin-15 mAb. Note the expression of keratin-15 (brown stain, green arrows) is colocalized with nestin-GFP in (a). Hemotoxylin counterstaining. Light microscopy. Magnification 400x. 

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