The ventral proximal nail fold: stem cell niche of the nail and equivalent to the follicular bulge--a study on developing human skin.
BACKGROUND
Although the bulge is well characterized as a stem cell niche of the hair follicle, comparatively little is known about the location of stem cells in the nail. Herein, we describe the spatiotemporal expression pattern of six stem cell markers in the developing human nail and compared it with the embryonic and fetal human hair follicle. The areas of proliferative activity were additionally examined using labeling with Ki-67.


METHODS
We examined immunohistochemically samples from embryonic and fetal human nail, hair and skin for the expression of cytokeratin 15 (CK15, two clones), cytokeratin 19 (CK19), PHLDA1, CD200, nestin and Ki-67 using standard techniques.


RESULTS
CK15 (clone LHK15), CK19 and PHLDA1 are negative in the nail and hair matrix but positive in the ventral proximal nail fold and in the follicular bulge. Over the course of embryogenesis they display a highly specific spatiotemporal expression pattern both in the nail and in the hair follicle.


CONCLUSIONS
We propose that at least during embryogenesis the proximal ventral nail fold represents the niche for the nail stem cells. In contrast to animal experiments, autoradiographic pulse-chasing studies cannot be performed in human, and immunohistochemical studies are a valid alternative although they have their limitations. Further studies on adult human nail units are suggested.
Department of Dermatology, Cleveland Clinic Foundation, Cleveland, OH, USA. klaus.sellheyer@gmail.com
Klaus
K
Sellheyer
Paula
P
Nelson
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D053569:Keratin-15 / Q000096:biosynthesis; D053539:Keratin-19 / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D009262:Nails / Q000166:cytology / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D064231:Nestin; D012867:Skin / Q000166:cytology / Q000196:embryology*; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007381:Intermediate Filament Proteins; D053569:Keratin-15; D053539:Keratin-19; D019394:Ki-67 Antigen; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C491923:PHLDA1 protein, human; D014157:Transcription Factors; C042739:antigens, CD200