A common progenitor gives rise to fibroblastic reticular cells and vascular smooth muscle cells in murine lymph nodes

The interaction of immune cells in the lymph node microenvironment depends on the infrastructure and molecular cues provided by fibroblastic reticular cells (FRCs). In addition, concentric layers of still poorly defined mural cells, including vascular smooth muscle cells (VSMCs), are involved in positioning and regulating immune cell interactions in different lymph node compartments. Using time-resolved single-cell transcriptomics, combined with cell fate mapping and high-resolution confocal microscopy, we found that lymph node FRCs and VSMCs share a proliferating, CCL19-expressing embryonic progenitor. Trajectory analysis identified lymphotoxin β receptor (LTβR)-dependent lineages that gave rise to FRCs underpinning the subcapsular sinus, T and B cell zones, and the medulla. LTβR-independent development of VSMCs and perivascular reticular cells from the common progenitor highlighted the close developmental relationship between FRCs and mural cells. Collectively, these results indicate that CCL19-expressing perivascular progenitors are capable of generating the fibroblastic and mural cell infrastructure of murine lymph nodes.