(F1003) Clear distinctions between mesenchymal stromal cells and pericytes derived from mouse lung tissue revealed by a single cell transcriptomic analysis
Tasly Group Tianjin, Tianjin, China (People's Republic)
Abstract: The distinct identity of mesenchymal stromal cells (MSCs) versus pericytes remains unknown, but both are reported to be associated with endothelial cells, regulating the permeability of capillary vascular system. The present study was undertaken to unveil the distinctions between MSCs and pericytes by a single-cell transcriptomic analysis. Mouse lung tissue was obtained via thoracotomy, and the bulk of all different cells from the entire tissue was subjected to scRNA-seq analysis. Single-cell functional gene expression was analyzed to identify MSCs by Tmem119, Fbln5, Kcnk2, Cldn11, and Dkk1, and pericytes by Pdgfrb, Cspg4, Cox4i2, Kcnk3 and Ndufa4l2. There were about 0.01% of MSCs and 1% of pericytes in the overall lung tissue cell populations. After these cells were cultured for 3 passages, the MSCs were increased to 5% of the total populations and the pericytes remained the same proportion. There were about 80% of MSCs expressing genes enriched in mitosis and cell cycle regulation pathways, and 20% of MSCs sharing a global gene expression profile with that of pericytes, with genes enriched in the PDGF signaling and extracellular matrix degradation pathways. Single-cell trajectory analysis revealed that MSCs and pericytes trailed different developmental lineages reaching at distinct terminal stages of differentiation, indicating a parallel rather than sequential differentiation paths between MSCs and pericytes. In addition, MSCs displayed a farther developmental cliff than that of pericytes from embryonic stem cells. Cell–cell communication analysis based on single-cell transcriptomic enrichment identified that cultured MSCs secreted FBLN5, CLDN11, and TMEM119, stimulating pericytes to release tissue repair and angiogenesis signals, including TIMP, PDGF, Cxcl12, and VEGFA. This study thus unveils clear distinctions between MSCs and pericytes, and in the lung, pericytes would be the majority of cells associated with endothelial cells for the regulation of vascular permeability. However, MSCs would play a stimulatory action on pericytes for their function of angiogenesis, but MSCs and pericytes trail distinct lineages from development hierarchy.
