Background Pericytes are perivascular cells that contribute to vascular homeostasis, tissue repair, and microenvironmental regulation. Increasing evidence suggests that pericytes share phenotypic and functional features with mesenchymal stromal cells (MSCs), although the extent of this relationship and its conservation across tissues remain poorly understood. In particular, whether distinct pericyte subpopulations exhibit differential mesenchymal characteristics depending on tissue context has not been systematically investigated. Methods CD146-positive and CD146-negative pericyte populations were isolated from murine brain and lung microvasculature using magnetic cell sorting. Canonical pericyte markers (PDGFRβ, RGS5, NG2 and α-SMA), endothelial and hematopoietic markers (CD31, CD34 and CD45), and mesenchymal-associated markers (CD90, CD44 and CD105) were analyzed by multiparametric flow cytometry to compare pericyte subsets across tissues. Results CD146 identified distinct non-endothelial pericyte populations in both brain and lung tissues. In both organs, CD146 + pericytes exhibited increased expression of mesenchymal-associated markers compared with their CD146 - counterparts, supporting the presence of a conserved mesenchymal-like pericyte compartment. However, the organization of this phenotype differed between tissues. Brain-derived pericytes displayed significantly higher expression of RGS5, α-SMA and NG2 than lung-derived pericytes, indicating tissue-specific differences in canonical pericyte identity. Within the mesenchymal-associated compartment, CD90 emerged as the principal marker distinguishing CD146 + pericytes, whereas CD44 and CD105 remained broadly expressed across pericyte populations from both tissues. Conclusion Our findings support the concept that pericytes constitute a heterogeneous component of the mesenchymal stromal cell compartment while preserving a conserved mesenchymal-associated core across tissues. Comparative analysis of brain- and lung-derived pericytes revealed that, despite sharing key mesenchymal-associated characteristics, these populations differ in the organization of both canonical pericyte markers and mesenchymal-associated features. These findings provide new insight into pericyte heterogeneity and establish a comparative framework for investigating how tissue-specific pericyte states contribute to tissue homeostasis and disease.
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Martínez et al. (2026) studied this question.
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