ABSTRACT: Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs (e.g., PDGFRB, NGFR, CSPG4, ACTA2, ALPL, NESTIN, LEPR, CXCL12, SEPT4, and GLI1), but also of AT stem/progenitor cells previously described in mice (BHLHE22, ZNF423, CYP7B1, FABP4, PPARG, and CD34). Additional analyses defined a gene expression signature for AT PCs, and revealed putative novel AT PC markers (e.g., APOD, ARC, SPARCL1, OMD, IGF1, EDNRB, and TNMD). Various transcripts, including NGFR, LEPR, and almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded PCs. Genes expressed by ATMSCs but not by ATPCs (e.g., CDH2, SSTR1, and FGF1) were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology.
