Abstract
Mesenchymal cells are important components of specified niches in the lung, and can mediate a wide range of processes including tissue regeneration and repair. Dysregulation of these processes can lead to improper remodeling of tissue as observed in several lung diseases. The mesenchymal cells responsible remain poorly described, partially due to the heterogenic nature of the mesenchymal compartment and the absence of appropriate markers. Here, we describe that CD105+CD90+ mesenchymal cells can be divided into two populations based on their expression of CD13/aminopeptidase N (CD105+CD90+CD13− and CD105+CD90+CD13+). By prospective isolation using FACS, we show that both these populations give rise to clonogenic fibroblast-like cells, but with an increased clonogenic and proliferative capacity of CD105+CD90+CD13+ cells. Transcriptomic and spatial analysis pinpoints an adventitial fibroblast subset as the origin of CD105+CD90+CD13+ clonogenic mesenchymal cells in human lung.
Highlights
Mesenchymal cells are important components of specified niches in the lung, and can mediate a wide range of processes including tissue regeneration and repair
We describe the isolation and enrichment of a subset of adventitial mesenchymal cells with clonogenic potential based on CD105+CD90+CD13+ expression
We observed that this population had an increased frequency of clonogenic cells and showed an increased proliferative potential compared to C D105+CD90+ mesenchymal cells which lacked CD13 expression, suggesting functional differences between these phenotypes
Summary
Mesenchymal cells are important components of specified niches in the lung, and can mediate a wide range of processes including tissue regeneration and repair. Different mesenchymal cell types have been described using a large variety of terminology and marker combinations, there is a large overlap in surface marker profile making them difficult to isolate and study. This is partly due to the great level of plasticity of mesenchymal cells depending on microenvironmental cues[9,10]. It is not surprising that some markers, originally identified in in vitro cultures, are differently expressed on uncultured primary cell p opulations[11,12] These culture-induced changes are likely to affect cellular function and behavior and obscure true heterogeneity of native mesenchymal cells. To uncover specific cellular functions within this heterogeneous cell pool, novel markers are needed that further separate primary, uncultured mesenchymal cell populations
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