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

ABSTRACT: Global expression analysis of neural crest-like skin-derived precursors (SKPs) and Sox2-positive follicle dermal cells that SKPs originate from. In spite of the remarkable regenerative capacity of mammalian skin, an adult dermal stem cell has not yet been identified. Here, we provide evidence that SKPs, multipotent neural crest-like skin-derived precursors, represent an adult dermal stem cell. When transplanted into adult skin, SKPs can reconstitute the adult dermis, contribute to dermal wound-healing, home to a hair follicle niche, and instruct epidermal cells to make hair follicles. Hair follicle-derived SKPs self-renew, maintain their multipotency, and serially reconstitute hair follicles. The endogenous origin of SKPs are Sox2-positive follicle dermal cells that share a similar global gene expression profile with SKPs. These endogenous cells home back to their follicle niche, induce hair follicle morphogenesis, and differentiate into neural and dermal progeny. Hair follicle-associated dermal cells will move out of their niche to contribute to dermal maintenance and wound-healing. These studies therefore identify a dermal stem cell, and provide a biological rationale for the presence of a multipotent precursor within adult dermis, findings with important therapeutic implications.

ORGANISM(S): Mus musculus

PROVIDER: GSE18690 | GEO | 2009/10/23

SECONDARY ACCESSION(S): PRJNA121475

REPOSITORIES: GEO

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Project description:Hair follicle formation depends on reciprocal epidermal-dermal interactions and occurs during skin development, but not in adult life. This suggests that the properties of dermal fibroblasts change during postnatal development. To examine this, we used a PdgfraEGFP mouse line to isolate GFP-positive fibroblasts from neonatal skin, adult telogen and anagen skin and adult skin in which ectopic hair follicles had been induced (EF skin) by transgenic epidermal activation of beta-catenin. We also isolated epidermal cells from each mouse. The gene expression profile of EF epidermis was most similar to that of anagen epidermis, consistent with activation of beta-catenin signalling. In contrast, adult dermis with ectopic hair follicles more closely resembled neonatal dermis than adult telogen or anagen dermis. In particular, genes associated with mitosis were upregulated and extracellular matrix-associated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal beta-catenin activation stimulated fibroblasts to proliferate to reach the high cell density of neonatal skin. In addition, the extracellular matrix was comprehensively remodelled, with mature collagen being replaced by collagen subtypes normally present only in developing skin. The changes in proliferation and extracellular matrix composition originated from a specific subpopulation of fibroblasts located beneath the sebaceous gland. Our results show that adult dermis is an unexpectedly plastic tissue that can be reprogrammed to acquire the molecular, cellular and structural characteristics of neonatal dermis in response to cues from the overlying epidermis. We have isolated the following populations of cells from mouse back skin by flow cytometry: 1A) GFP+ WT neonatal dermal fibroblasts, 1B) ItgA6+ WT neonatal epidermal keratinocytes, 2A) GFP+ WT telogen dermal fibroblasts, 2B) ItgA6+ WT telogen epidermal keratinocytes, 3A) GFP+ D2 transient activation (anagen) dermal fibroblasts, 3B) ItgA6+ D2 transient activation (anagen) epidermal keratinocytes, 4A) GFP+ D2 sustained activation (ectopic follicles) dermal fibroblasts, 4B) ItgA6+ D2 sustained activation (ectopic follicles) epidermal keratinocytes

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

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