PDGFRa and aSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

Adventitial fibroblasts direct smooth muscle cell-state transition in pulmonary vascular disease

“…In this OPLA-DA model, only in the case of transcriptomic dataset there was significant separation between all four groups (Figure 2C). These results imply that remodeling process results in substantial transcriptional changes (cell-state), but that each cell type retains their original cell lineage designation, in line with results from fate mapping and fresh cell single cell transcriptomics 4,6,20 . Gene ontology analysis of selected gene sets from combined transcriptomic and proteomic data (significantly regulated genes/proteins, Figure 2D), showed a cell-type specific footprint of molecular changes upon IPAH (Figure 2E).…”

“…Additional layer of cellular complexity and heterogeneity is acquired through the disease process. Vascular smooth muscle cells and adventitial fibroblasts preserve their lineage identity in animal models of systemic and pulmonary vascular disease [5][6][7][8][9][10] . However, diseased cells consistently display altered expression profiles compared to their healthy counterparts 4,9,10 .…”

A census of the lung: CellCards from LungMAP

“…Key references: Chen et al, 2012; Barkauskas et al, 2013;Hung et al, 2013;Lee et al, 2017;Zepp et al, 2017Zepp et al, , 2021Kato et al, 2018;Biasin et al, 2020).…”

Identification of a Repair-Supportive Mesenchymal Cell Population during Airway Epithelial Regeneration

“…Those cells partially expressed Acta2 at day 7 (Figure S2A), were present at varying extents along the non-cartilaginous conducting airway, and were mostly observed between the ASMC sheet and the airway epithelium around the proximal lobular airways and at branch points. Because peribronchial PDGFRa + cells are primed to differentiate along the ASMC lineage during embryonic development (El Agha et al, 2014;Andrae et al, 2014;Cohen et al, 2009;Endale et al, 2017;Gouveia et al, 2017;Ntokou et al, 2015), and based on recent work showing that PDGFRa and ACTA2 mark distinct populations of mesenchymal cells in the remodeled lung (Biasin et al, 2020), we decided to check whether those non-ASMC-lineage-labeled cells express Pdgfra. Indeed, immunofluorescence showed that 74% of those peribronchial non-ASMC-lineage-labeled cells were PDGFRa + (Figures 2E, 2F, and 2N), whereas the expression of PDGFRa was very weak in oil-treated samples (Figures 2B and 2C).…”