Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons.
We have recently shown that the expression of nestin, the neural stem cell marker protein, is expressed in bulge-area stem cells of the hair follicle. We used transgenic mice with GFP expression driven by the nestin regulatory element [nestin-driven GFP (ND-GFP)]. The ND-GFP stem cells give rise to the outer-root sheath of the hair follicle as well as an ND-GFP interfollicular vascular network. In this study, we demonstrate that ND-GFP stem cells isolated from the hair-follicle bulge area that are negative for the keratinocyte marker keratin 15 can differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. These pluripotent ND-GFP stem cells are positive for the stem cell marker CD34, as well as keratin 15-negative, suggesting their relatively undifferentiated state. The apparent primitive state of the ND-GFP stem cells is compatible with their pluripotency. Furthermore, we show that cells derived from ND-GFP stem cells can differentiate into neurons after transplantation to the subcutis of nude mice. These results suggest that hair-follicle bulge-area ND-GFP stem cells may provide an accessible, autologous source of undifferentiated multipotent stem cells for therapeutic application.
Amoh
Yasuyuki
Y
AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, USA.
Li
Lingna
L
Katsuoka
Kensei
K
Penman
Sheldon
S
Hoffman
Robert M
RM
D000818:Animals; D002454:Cell Differentiation; D017690:Cell Transplantation; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000032:analysis*; D007633:Keratins / Q000032:analysis*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D009419:Nerve Tissue Proteins / Q000032:analysis*; D064231:Nestin; D009474:Neurons / Q000166:cytology* / Q000378:metabolism
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D007633:Keratins