Reprogramming adult dermis to a neonatal state through epidermal activation of β-catenin

Abstract

SUMMARYHair 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 by transgenic epidermal activation of b-catenin (EF skin). 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 b-catenin signalling. By 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 matrixassociated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal b-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.

Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells

“…We also examined dermal cell behavior by observing Pdgfra-EGFP mouse cells (Movie S3), which represent all dermal cell lineages (26). Six major stages were observed comparable to the stages in epidermal cells ( iv) Reorganization: As the epidermal cysts merge, the dermal cells move away from the interaggregate region (Movies S2B and S3).…”

Estrogen modulates mesenchyme-epidermis interactions in the adult nipple

“…Platelet-derived growth factor receptor α (Pdgfrα) was previously reported to be a useful marker for isolating dermal fibroblasts from haired skin (Collins et al, 2011). Here, by using immunofluorescence, we show that Pdgfrα is expressed in nipple fibroblasts, but not in basal keratinocytes in WT ventral skin.…”

“…3A). To purify cells expressing high amounts of CD140 (the CD140 hi population), we set up a dump channel to exclude cells expressing CD31 (endothelial cells), CD117 (melanocytes), CD45 (hematopoietic cells) or CD49f markers (keratinocytes) (Collins et al, 2011 Fig. 3D) (Kalluri and Zeisberg, 2006).…”

“…The isolated cells were labeled with anti-mouse CD140a-APC (17-1401-81, eBioscience), anti-mouse CD31-(PECAM-1)-PE (12-0311, eBioscience), anti-mouse CD45-PE (12-045, eBioscience), anti-mouse CD117-(c-kit)-PE (12-1171, eBioscience) and anti-human/anti-mouse CD49f-(Integrin α6)-PE (12-0495, eBioscience) (Collins et al, 2011) (antibodies were used according to the manufacturer's instruction). Meanwhile, 7-aminoactinomycin D (7-AAD) viability staining was performed to exclude dead cells.…”

Genetic mouse models for skin research: Strategies and resources

“…FDP cells regulate hair follicle development and growth, and the prospect of employing these cells for the therapy of hair growth disorders resulted in a growing interest in their biology (Driskell et al, 2011;Yang and Cotsarelis, 2010). Different regulatory regions have been employed to identify and isolate FDP cells, including the human LEF1 promoter (Rendl et al, 2005(Rendl et al, , 2008 and the endogenous Sox2 (Biernaskie et al, 2009) and platelet-derived growth factor receptor-a (Collins et al, 2011) loci. More specific targeting of dermal cells can be obtained with the versican promoter (Kishimoto et al, 1999), which directs expression to the dermal papilla in postnatal mice and to its precursor structures during embryonic development.…”