Context-Dependent Development of Lymphoid Stroma from Adult CD34+ Adventitial Progenitors
Graphical Abstract Highlights d CD34 + stromal cells localize to the adventitial vascular niche in lymphoid tissues d Thymic CD34 + cells and pericytes derive from a common anlage-seeding population d Adult CD34 + adventitial cells have lymphoid stroma-like progenitor potential d Lymphoid environment regulates the differentiation of CD34 + adventitial progenitors SUMMARY Despite the key role of primary and secondary lymphoid organ stroma in immunity, our understanding of the heterogeneity and
... heterogeneity and ontogeny of these cells remains limited. Here, we identify a functionally distinct subset of BP3 À PDPN + PDGFRb + /a + CD34 + stromal adventitial cells in both lymph nodes (LNs) and thymus that is located within the vascular niche surrounding PDPN À PDGFRb + /a À Esam-1 + ITGA7 + pericytes. CD34 + adventitial cells developed in late embryonic thymus and in postnatal LNs and in the thymus originated, along with pericytes, from a common anlage-seeding progenitor population. Using lymphoid organ re-aggregate grafts, we demonstrate that adult CD34 + adventitial cells are capable of differentiating into multiple lymphoid stroma-like subsets including pericyte-, FRC-, MRC-, and FDClike cells, the development of which was lymphoid environment-dependent. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34 + adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues.