SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells.

Despite the remarkable regenerative capacity of mammalian skin, an adult dermal stem cell has not yet been identified. Here, we investigated whether skin-derived precursors (SKPs) might fulfill such a role. We show that SKPs derive from Sox2(+) hair follicle dermal cells and that these two cell populations are similar with regard to their transcriptome and functional properties. Both clonal SKPs and endogenous Sox2(+) cells induce hair morphogenesis, differentiate into dermal cell types, and home to a hair follicle niche upon transplantation. Moreover, hair follicle-derived SKPs self-renew, maintain their multipotency, and serially reconstitute hair follicles. Finally, grafting experiments show that follicle-associated dermal cells move out of their niche to contribute cells for dermal maintenance and wound-healing. Thus, SKPs derive from Sox2(+) follicle-associated dermal precursors and display functional properties predicted of a dermal stem cell, contributing to dermal maintenance, wound-healing, and hair follicle morphogenesis.

[1]  D. Tobin,et al.  Plasticity and cytokinetic dynamics of the hair follicle mesenchyme: implications for hair growth control. , 2003, The Journal of investigative dermatology.

[2]  K. McElwee,et al.  Cultured peribulbar dermal sheath cells can induce hair follicle development and contribute to the dermal sheath and dermal papilla. , 2003, The Journal of investigative dermatology.

[3]  F. Miller,et al.  Isolation of skin-derived precursors (SKPs) and differentiation and enrichment of their Schwann cell progeny , 2006, Nature Protocols.

[4]  Gordon K Smyth,et al.  Statistical Applications in Genetics and Molecular Biology Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments , 2011 .

[5]  C. Jahoda,et al.  Hair follicle stem cells. , 2007, Seminars in cell & developmental biology.

[6]  Jeff Biernaskie,et al.  Skin-Derived Precursors Generate Myelinating Schwann Cells for the Injured and Dysmyelinated Nervous System , 2006, The Journal of Neuroscience.

[7]  Ying Zheng,et al.  Organogenesis from dissociated cells: generation of mature cycling hair follicles from skin-derived cells. , 2005, The Journal of investigative dermatology.

[8]  R. Oliver.  The experimental induction of whisker growth in the hooded rat by implantation of dermal papillae. , 1967, Journal of embryology and experimental morphology.

[9]  D. Fisher,et al.  Mechanisms of Hair Graying: Incomplete Melanocyte Stem Cell Maintenance in the Niche , 2005, Science.

[10]  Mahendra Rao,et al.  SOX2, a Persistent Marker for Multipotential Neural Stem Cells Derived from Embryonic Stem Cells, the Embryo or the Adult , 2004, Developmental Neuroscience.

[11]  David R. Kaplan,et al.  A dermal niche for multipotent adult skin-derived precursor cells , 2004, Nature Cell Biology.

[12]  W. Fox.  Cellular Contribution from Dermis and Cartilage to the Regenerating Limb Blastema in Axolotls , 2003 .

[13]  B. Hall,et al.  Development of the dermal skeleton in Alligator mississippiensis (Archosauria, Crocodylia) with comments on the homology of osteoderms , 2008, Journal of morphology.

[14]  S. Weiss,et al.  Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. , 1992, Science.

[15]  B. Alman,et al.  Skin-derived precursors differentiate into skeletogenic cell types and contribute to bone repair. , 2009, Stem cells and development.

[16]  D. Kaplan,et al.  Analysis of the neurogenic potential of multipotent skin-derived precursors , 2006, Experimental Neurology.

[17]  E. Markiewicz,et al.  C/EBPα identifies differentiating preadipocytes around hair follicles in foetal and neonatal rat and mouse skin , 2008, Experimental dermatology.

[18]  R. Oliver,et al.  Induction of hair growth by implantation of cultured dermal papilla cells , 1984, Nature.

[19]  S. Chandran,et al.  A Highly Enriched Niche of Precursor Cells with Neuronal and Glial Potential Within the Hair Follicle Dermal Papilla of Adult Skin , 2008, Stem cells.

[20]  C. Jahoda,et al.  Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages , 2003, Experimental dermatology.

[21]  M. Ikawa,et al.  Generating green fluorescent mice by germline transmission of green fluorescent ES cells , 1998, Mechanisms of Development.

[22]  E. A. Wright,et al.  A quantitative study of hair growth using mouse and rat vibrissal follicles. I. Dermal papilla volume determines hair volume. , 1982, Journal of embryology and experimental morphology.

[23]  C. Jahoda,et al.  Plasticity of hair follicle dermal cells in wound healing and induction , 2003, Experimental dermatology.

[24]  Elly M. Tanaka,et al.  Cells keep a memory of their tissue origin during axolotl limb regeneration , 2009, Nature.

[25]  E. Fuchs.  Finding one's niche in the skin. , 2009, Cell stem cell.

[26]  S. Chandran,et al.  Efficient generation of neural precursors from adult human skin: astrocytes promote neurogenesis from skin-derived stem cells , 2004, The Lancet.

[27]  F. Watt,et al.  Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis , 2009, Development.

[28]  R. Lovell-Badge,et al.  Multipotent cell lineages in early mouse development depend on SOX2 function. , 2003, Genes & development.