Fingernail Stem Cell Population Identified


The ability of fingernails to grow back, unlike other body parts seems to be the result of the presence of a resident stem cells population.

Researchers at the University of Southern California (USC), led by Krzysztof Kobielak has identified a new stem population in nails that can either self-renew or differentiate into other distinct cell types.

Identifying these cells was no small chore, and Kobielak used an ingenious new technique for attaching fluorescent dyes and other tags to mouse nail cells. while many cells in the nail divided and spread throughout the nail, another small population stayed at the base of the nail and divided slowly or not at all.

Localization of LRCs in the nail proximal fold. (A) Components of the mouse nail. Top view, horizontal sections of the fingertip before (C) and after (B and D) 4 wk of chase with Dox identifying a population of H2BGFP marked LRCs surrounding the nail structure. Side view, perpendicular sections of the digit tip before (E and G) and after (F) 4 wk of chase with Dox demonstrating the presence of upper LRCs in the upper PF. (H) Lower LRCs at the lower nail PF. GFP; green fluorescent protein; HF, hair follicle; L-LRCs, lower label-retaining cells; U-LRCs, upper label-retaining cells. Yellow box denotes region of interest in B, and red and blue boxes (G) denote representative U-PF and L-PF regions for orientation. (Scale bars: 50 μm.)
Localization of LRCs in the nail proximal fold. (A) Components of the mouse nail. Top view, horizontal sections of the fingertip before (C) and after (B and D) 4 wk of chase with Dox identifying a population of H2BGFP marked LRCs surrounding the nail structure. Side view, perpendicular sections of the digit tip before (E and G) and after (F) 4 wk of chase with Dox demonstrating the presence of upper LRCs in the upper PF. (H) Lower LRCs at the lower nail PF. GFP; green fluorescent protein; HF, hair follicle; L-LRCs, lower label-retaining cells; U-LRCs, upper label-retaining cells. Yellow box denotes region of interest in B, and red and blue boxes (G) denote representative U-PF and L-PF regions for orientation. (Scale bars: 50 μm.)

Kobielak and his team showed that these slow-dividing cells normally contribute to the growth of her nails and nearby skin. However, if the nail undergoes some kind of injury or physical insult, a signaling protein called bone morphogen protein or BMP signals to the nail bed stem cells to switch to exclusively repairing the nail. Thus this nail bed stem cell population has the flexibility to perform dual roles in the finger tips.

Nail proximal fold cells participate in nail regeneration in response to plucking injury and upon transplantation. (A) Whole-mount Tomato expression in regenerated nails 2 wk after plucking. Linear streams of Tomato+ cells (red) in regenerating nails (arrows) extending from the nail base toward the tip. (B) Schematic model representing the role of K15+ NPFSCs during nail regeneration. (C–C′′) K5 expression (green) in regenerating nails localizing the linear K15-derived, Tomato+ (red) cell streams emanating from the basal K5+ Mx extending upward (arrows) into the overlying differentiated NP; yellow box denotes region of interest in (C′ and C′′). (D) H2BGFP+ nail LRCs persist in the finger following nail removal. (E) Nail LRCs are quiescent, whereas the nail Mx contains actively proliferating cells marked by BrdU incorporation. (F) Upon NP removal, LRCs become activated, indicated by Ki67 coexpression. (G) Nail LRCs transplantation strategy. H2BGFP+ nail cells contribute to the nail structure 17 d after transplantation (H), sectioning of 22-d chased transplant (I), demonstrating the presence of remaining LRCs from the transplant. d, day; Epi, epidermis; GFP, green fluorescent protein; L-LRCs, lower label-retaining cells; U-LRCs, upper label-retaining cells. DAPI counterstaining (blue) was used to localize cell nuclei in immunofluorescent images. (Scale bars: A and H, 500 μm; C–F and I, 50 μm.)
Nail proximal fold cells participate in nail regeneration in response to plucking injury and upon transplantation. (A) Whole-mount Tomato expression in regenerated nails 2 wk after plucking. Linear streams of Tomato+ cells (red) in regenerating nails (arrows) extending from the nail base toward the tip. (B) Schematic model representing the role of K15+ NPFSCs during nail regeneration. (C–C′′) K5 expression (green) in regenerating nails localizing the linear K15-derived, Tomato+ (red) cell streams emanating from the basal K5+ Mx extending upward (arrows) into the overlying differentiated NP; yellow box denotes region of interest in (C′ and C′′). (D) H2BGFP+ nail LRCs persist in the finger following nail removal. (E) Nail LRCs are quiescent, whereas the nail Mx contains actively proliferating cells marked by BrdU incorporation. (F) Upon NP removal, LRCs become activated, indicated by Ki67 coexpression. (G) Nail LRCs transplantation strategy. H2BGFP+ nail cells contribute to the nail structure 17 d after transplantation (H), sectioning of 22-d chased transplant (I), demonstrating the presence of remaining LRCs from the transplant. d, day; Epi, epidermis; GFP, green fluorescent protein; L-LRCs, lower label-retaining cells; U-LRCs, upper label-retaining cells. DAPI counterstaining (blue) was used to localize cell nuclei in immunofluorescent images. (Scale bars: A and H, 500 μm; C–F and I, 50 μm.)

The members of the Kobielak laboratory are also interested in other types of signals and what they might do to these nail bed stem cells. For example, could they induce them to differentiate into additional cell types besides skin and nail? Could they aid in amputation repair and the repair of severe skin injuries?

Kobielak said: “That was very surprising discovery [sic], since the dual characteristics of these nail stem cells to regenerate both the nail and the skin under certain physiological conditions is quite unique and different from other skin stem cells, such as those of the hair follicle or sweat gland.”

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