A role for pericytes as microenvironmental regulators of human skin tissue regeneration

Abstract

The cellular and molecular microenvironment of epithelial stem and progenitor cells is poorly characterized despite well-documented roles in homeostatic tissue renewal, wound healing, and cancer progression. Here, we demonstrate that, in organotypic cocultures, dermal pericytes substantially enhanced the intrinsically low tissue-regenerative capacity of human epidermal cells that have committed to differentiate and that this enhancement was independent of angiogenesis. We used microarray analysis to identify genes expressed by human dermal pericytes that could potentially promote epidermal regeneration. Using this approach, we identified as a candidate the gene LAMA5, which encodes laminin α5, a subunit of the ECM component laminin-511/521 (LM-511/521). LAMA5 was of particular interest as we had previously shown that it promotes skin regeneration both in vitro and in vivo. Analysis using immunogold localization revealed that pericytes synthesized and secreted LAMA5 in human skin. Consistent with this observation, coculture with pericytes enhanced LM-511/521 deposition in the dermal-epidermal junction of organotypic cultures. We further showed that skin pericytes could also act as mesenchymal stem cells, exhibiting the capacity to differentiate into bone, fat, and cartilage lineages in vitro. This study suggests that pericytes represent a potent stem cell population in the skin that is capable of modifying the ECM microenvironment and promoting epidermal tissue renewal from non-stem cells, a previously unsuspected role for pericytes.

End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data

“…6A; Supplemental Fig. S5): While gene ontology analysis shows strong enrichment in vascular development for clusters C4 and C9 (Supplemental Table S3), manual inspection of cluster-specific genes revealed that C4 cells specifically express pericyte markers (Paquet-Fifield et al 2009), while …”

Perivascular Ancestors of Adult Multipotent Stem Cells

“…15 Human pericytes also express alkaline phosphatase and the human dermis 1 antigen. 16,17 Fluorescence-activated cell sorter-purified pericytes were readily myogenic in culture and after injection into cardiotoxin-injured or genetically dystrophic severe combined immunodeficient mouse skeletal muscles. Pericytes grow proficiently in culture, exhibiting the morphology, mitotic activity, and surface antigens of MSCs (eg, CD44, CD73, CD90, and CD105).…”

Guanylate-binding protein 1 (GBP1) contributes to the immunity of human mesenchymal stromal cells against Toxoplasma gondii

“…MSCs have been successfully used to prevent and treat immune disorders, such as graft-versus-host disease, and emerging preclinical studies suggest that they might also protect against infectious challenges (1,2). Recent studies showed that MSCs are located in the perivascular niche and constitute a subset of pericytes that are involved in both pathogen recognition and early inflammatory events (3). MSCs seem to impede pathogen growth and reduce the microbial burden by inhibiting growth through soluble factors or by enhancing the antimicrobial function of immune cells, as shown both in vitro and in vivo (2)(3)(4)(5).…”

“…Recent studies showed that MSCs are located in the perivascular niche and constitute a subset of pericytes that are involved in both pathogen recognition and early inflammatory events (3). MSCs seem to impede pathogen growth and reduce the microbial burden by inhibiting growth through soluble factors or by enhancing the antimicrobial function of immune cells, as shown both in vitro and in vivo (2)(3)(4)(5). For example, Nemeth et al reported that mouse MSCs (mMSCs) prolonged the survival of septic mice and improved their organ (kidney, liver, and pancreas) functions (5).…”