We have previously shown that the mesenchymal microenvironment of human skin particularly the introduction of dermal pericytes increases epithelial tissue regeneration in organotypic cultures, even from non-stem cell populations of keratinocytes already committed to differentiate. This led us to speculate that factors secreted by pericytes are capable of promoting skin tissue regeneration. Since it is well-known that the regenerative capacity of skin diminishes with age in humans, we sought to investigate the differential gene expression profiles of young versus aged dermal cell populations particularly pericytes and fibroblasts in order to gain a better understanding of the molecular players involved in skin regeneration.
In this study we evaluated the transcriptomes of neonatal and adult human skin pericytes (validated by us previously as CD45-α1β1/VLA-1bri) and fibroblasts (CD45-α1β1/VLA-1dim) isolated from healthy donors using Human Gene 1.0 ST microarrays. Interestingly, despite the heterogeneity across donor samples, only 25 genes were identified as significantly differentially expressed (21 upregulated; 4 downregulated; P<0.05, cut-off of 2 fold change in expression) in neonatal versus adult pericytes; whereas 98 genes were altered in neonatal versus adult fibroblasts (80 up- and 18 downregulated). Gene Ontology analyses revealed enrichment for genes related to the biological processes of tissue remodelling and wound repair (e.g. extracellular matrix remodeling and cell adhesion) in neonatal pericytes whose expression was lost as a function of age.
Our data reveals novel candidate age-related pericyte-expressed genes and associated pathways involved in skin regeneration, that are currently being validated in functional assays of keratinocyte proliferation and skin tissue regeneration using monolayer as well as 3D organotypic cultures.