Abstract
The splenic white pulp is underpinned by poorly characterized stromal cells that demarcate distinct immune cell microenvironments. Here, definition of the embryonic origin and tracing of the differentiation trajectories of fibroblastic reticular cells (FRCs) was enabled by the establishment of FRC-specific fate-mapping in mice. We found that all reticular cell subsets descend from pluripotent progenitors that emerge at embryonic day 19.5 from Sca-1 periarterial progenitors. Commitment of FRC progenitors was concluded during the first week of postnatal life through occupation of niches along developing central arterioles. Single cell transcriptomic analysis facilitated deconvolution of FRC differentiation trajectories and indicated that perivascular reticular cells function both as adult lymphoid organizer cells and mural cell progenitors. Finally, the lymphotoxin-β receptor-independent sustenance of postnatal progenitor stemness unveiled that systemic immune surveillance in the splenic white pulp is governed through subset specification of reticular cells from a pluripotent periarterial progenitor cell.
Highlights
The splenic white pulp is underpinned by poorly characterized stromal cells that demarcate distinct immune cell microenvironments
Single cell transcriptomic analysis facilitated deconvolution of fibroblastic reticular cell (FRC) differentiation trajectories and indicated that perivascular reticular cells function both as adult lymphoid organizer cells and mural cell progenitors
Generation of functional immune environments in lymph nodes depends on maturation and functional specialization of fibroblastic reticular cells (FRC) that are associated with the broad expression of the mucin-type transmembrane protein podoplanin (PDPN)[12,13,14]
Summary
The splenic white pulp is underpinned by poorly characterized stromal cells that demarcate distinct immune cell microenvironments. The lymphotoxin- receptorindependent sustenance of postnatal progenitor stemness unveils that systemic immune surveillance in the splenic white pulp is governed through subset specification of reticular cells from a multipotent periarterial progenitor cell. The lymphotoxin-β receptor-independent sustenance of postnatal progenitor stemness unveils that systemic immune surveillance in the splenic white pulp is governed through subset specification of reticular cells from a multipotent periarterial progenitor cell. The analysis of cellular lineage relationship requires knowledge on the embryonic origin and subsequent commitment steps that determine the critical nodes in the differentiation trajectories Both red and white pulp fibroblastic stromal cells descend from stem cells in the embryonic splenopancreatic mesenchyme[2]. It is conceivable that the critical process of white pulp reticular cell progenitor commitment ensues during later stages of spleen development and that these cells may function as the main drivers for the structural organization of the white pulp
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
