Thymic Mesenchymal Cells Have a Distinct Transcriptomic Profile

Abstract

In order to understand the role of mesenchymal cells (MCs) in the adult thymus, we performed whole transcriptome analyses of primary thymic, bone, and skin MCs. These three MC populations shared expression of 2850 core MC genes involved in generic processes including interactions with tissue-resident macrophages. Moreover, we discovered that 2036 genes were differentially expressed, by at least 5-fold, in the three MC populations. Genes preferentially expressed in thymic MCs are instrumental in clearance of apoptotic thymocytes by macrophages, maintenance of a noninflammatory milieu, and attraction-expansion of thymocyte progenitors. Thymic and bone MCs share other sets of differentially expressed genes implicated in resolution of inflammation and expansion of hematolymphoid progenitors. Consistent with the fact that thymic and skin MCs have to support epithelial cells, they express at higher levels genes mediating epithelial cell adhesion to basement membrane and mesenchymal–epithelial cross-talk. Differentially expressed genes preferentially expressed by bone MCs are connected to formation and remodeling of bone, whereas those preferentially expressed in skin MCs are involved in skin and hair follicle homeostasis. We conclude that MCs from different organs display substantial heterogeneity and that the transcriptome of thymic MCs is exquisitely suited for interactions with epithelial and hematolymphoid cells in an environment with a high apoptosis rate.