Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons

doi:10.1073/pnas.0501263102

Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons

^*AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111; ^†Department of Dermatology, Kitasato University School of Medicine, Sagamihara 228-8555, Japan; ^‡Department of Surgery, University of California, San Diego, CA 92103; and ^§Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139

Contributed by Sheldon Penman, March 2, 2005

Abstract

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.

Footnotes

↵ ¶ To whom correspondence should be sent at the * address. E-mail: all{at}anticancer.com.
Author contributions: Y.A., L.L., and R.M.H. designed research; Y.A. and L.L. performed research; Y.A., L.L., K.K., S.P., and R.M.H. analyzed data; and Y.A., S.P., and R.M.H. wrote the paper.
Abbreviations: SMA, smooth muscle actin; bFGF, basic FGF; ND-GFP, nestin-driven GFP; GFAP, glial fibrillary acidic protein.